19: Cell Division and the Cell Cycle - Biology

19: Cell Division and the Cell Cycle - Biology

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  • 19.1: Introduction
    Mitosis is the condensation of chromosomes from chromatin and their separation into dividing cells. Cytokinesis is the process that divides a cell into two new cells after duplicated chromosomes are safely on opposite sides of the cell. Mitosis and Cytokinesis together are a relatively short time in the cell cycle. While cell cycle times vary, imagine a cell that divides every 20 hours.
  • 19.2: Bacterial Cell Division and the Eukaryotic Cell Cycle
    The life of actively growing bacteria is not separated into a time for duplicating genes (i.e., DNA synthesis) and one for binary fission (dividing and partitioning the duplicated DNA into new cells). Instead, the single circular chromosmome of a typical bacterium is replicating even before fission is complete, so that the new daughter cells already contained partially duplicated chromosomes. Cell growth, replication and fission are illustrated below.
  • 19.3: Regulation of the Cell Cycle
    Progress through the cell cycle is regulated. The cycle can be controlled or put on ‘pause’ at any one of several phase transitions. Such checkpoints monitor whether the cell is on track to complete a successful cell division event. Superimposed on these controls are signals that promote cell differentiation.
  • 19.4: When Cells Die
    As noted, few cell types live forever; most live for a finite time. Most are destined to turn over (another euphemism for dying), mediated by programmed cell death, or apoptosis. This occurs in normal development when cells are only temporarily required for a maturation process (e.g., embryonic development, metamorphosis).
  • 19.5: Disruption of the Cell Cycle Checkpoints Can Cause Cancer
    If a checkpoint fails or if a cell suffers physical damage to chromosomes during cell division, or if it suffers a debilitating somatic mutation in a prior S phase, it may selfdestruct in response to a consequent biochemical anomaly. This is another example of apoptosis. On the other hand, when cells die from external injury, they undergo necrosis, an accidental rather than a programmed death.
  • 19.6: Key Words and Terms

Thumbnail: Life cycle of the cell. (CC BY-SA 4.0; BruceBlaus).​​​​​

Chapter 19 Outline - Summary The World of the Cell

 Proper control of cell division is vital to all organisms.  Cell division must be balanced with cell growth so the cell size is properly maintained. o If cells grow too large before division, they can function improperly or if division occurs before growth is completed the cells might not be viable.

 Precise control and timing  Loss of normal controls on cell replication is the fundamental defect in cancer.

Cell Cycle  ordered series of events that lead to cell division and the production of 2 daughter cells.  Chromosome replication and segregation to daughter cells must occur in the proper order in every cell division.

 G1  Cell in its normal every day life functioning  G0  Cells have been removed because they aren’t functioning properly  S  DNA synthesis / centrosome duplication  G2  prepare for division  M generate 2 daughter cells with the exact same genetic material and number of chromosomes

Surveillance Mechanisms: Checkpoint Pathways

 Mechanism that occurs at each phase to make sure you don’t start initiation of one step until the previous step is completed  Assures that the cell cycle is done properly  Check for damage in DNA  Mutations that inactive or alter the normal operation of these checkpoints contribute to the generation of cancer cells. o A lot of the proteins that regulate the cell cycle, are the same proteins that have mutations associated with cancer.

Master Controllers of the Cell Cycle = Cyclin Dependent Kinases

 CDK’s (catalytic subunit) have to associate with another protein called Cyclin (Regulatory subunit)  Cyclin Dependent Kinases + Cyclin are heterodimers (2 subunits together) o Cyclin – part regulated by protein levels (synthesis and degradation) o CDK’s – going to be controlled by phosporylation  Serine / Threonine Kinases

o For both of those to have activity, cyclin and CDK must come together to form a dimer.  CDKs are only active in the stages of the cell cycle they trigger.

 Control movement from one step to another  Act as checkpoints before you can move into the next step

 CDK’s regulate the activities of multiple proteins involved in entry into the cell cycle by phosphorylating them at specific regulatory sites, by activating some and inhibiting others to coordinate their activities.

 Control of CDK governs the events that take place in each phase.  We have different classes of CDK’s that are present in each set of the cell cycle

Previous Year Questions (2016-19) - Cell Cycle and Cell Division Notes | EduRev

Q.1. Identify the correct statement with regard to G1 phase (Gap I) of interphase (2020)
(a) Cell is metabolically active, grows but does not replicate its DNA
(b) Nuclear division takes place
(c) DNA synthesis or replication takes place
(d) Reorganisation of all cell components takes place

Ans. (a)
G1 Phase is metabolically active stage of cell cycle. Different type of amino acid RNA, Protein synthesis take place in G1 phase but DNA replication does not take place, (Note :- DNA replication occur in S-Phase)

Q.2. Dissolution of the synaptonemal complex occurs during: (2020)
(a) Diplotene
(b) Leptotene
(c) Pachytene
(d) Zygotene

Ans. (a)
Dissolution of the synaptonemal complex occurs at diplotene phase of prophase I in meiosis.

Q.3. Match the following with respect to meiosis: (2020)

Select the correct option from the following:

Ans. (d)
Terminalization: It is the stage in which chromosomes condenses further. Sites of crossing over entangle together with effective overlapping which makes chiasmata clearly visible.
Chiasmata: It is the region where crossing over occurs.
Crossing over: Crossing over or chromosomal crossover occurs in the pachytene stage in which non sister chromatids of homologous chromosomes may exchange segments over regions of homology.
Synapsis: Synapsis of homologous chromosomes takes place in the zygotene stage.

Q.4. Some dividing cells exit the cell cycle and enter vegetative inactive stage. This is called quiescent stage (G0). This process occurs at the end of : (2020)
(a) S phase
(b) G2 Phase
(c) M phase
(d) G1 phase

Ans. (c)
In M-Phase, some cells do not divide further exist G1 phase to enter an inactive stage called quiescent stages (G0) of the cell cycle.

Q.5. Cells in G0 phase (2019)
(a) Terminate the cell cycle
(b) Exit the cell cycle
(c) Enter the cell cycle
(d) Suspend the cell cycle.
Some cells in the adult animals do not appear to exhibit division (e.g., heart cells) and many other cells divide only occasionally, as needed to replace cells that have been lost because of injury or cell death. These cells that do not divide further exit G1 phase to enter an inactive stage called quiescent stage (G0) of the cell cycle. Cells in this stage remain metabolically active but no longer proliferate unless called on to do so depending on the requirement of the organism.

Q.6. The correct sequence of phases of cell cycle is (2019)
(a) G1 → S → G2 → M
(b) M → G1 → G2 → S
(c) G1 → G2 → S → M
(d) S → G1 → G2 → M


Q.7. Crossing over takes place between which chromatids and in which stage of the cell cycle? (2019)
(a) Non-sister chromatids of non-homologous chromosomes at Zygotene stage of prophase I.
(b) Non-sister chromatids of homologous chromosomes at Pachytene stage of prophase I.
(c) Non-sister chromatids of homologous chromosomes at Zygotene stage of prophase I.
(d) Non-sister chromatids of non-homologous chromosomes at Pachytene stage of prophase I.

Ans. (b)

Q.8. The stage during which separation of the paired homologous chromosomes begins is (2018)
(a) Pachytene
(b) Diplotene
(c) Diakinesis
(d) Zygotene
During diplotene, the nucleoprotein fusion complex of synapsed chromosomes dissolves partially therefore homologous chromosomes separate except in the region of crossing over.

Q.9. Which of the following options gives the correct sequence of events during mitosis? (2017)
(a) Condensation → Nuclear membrane disassembly → Arrangement at equator → Centromere division → Segregation → Telophase
(b) Condensation → Crossing over → Nuclear membrane disassembly → Segregation → Telophase
(c) Condensation → Arrangement at equator → Centromere division → Segregation → Telophase
(d) Condensation → Nuclear membrane disassembly → Crossing over → Segregation → Telophase
Mitosis is divided into four phase prophase, metaphase, anaphase and telophase. During prophase, the indistinct and intertwined DNA molecule condenses to form elongated chromosomes. The nuclear membrane disintegrates during prometaphase During metaphase, the chromosomes align themselves at the equatorial plate. During anaphase, centromere of each chromosome divides into two so that each chromosome come to have its own centromere Chromatids move towards opposite poles along the path of their chromosome fibres. Finally, during telophase, two chromosome groups reorganise to form two nuclei. Nuclear envelope reappears, Golgi complex and endoplasmic reticulum are reformed Crossing over occurs during meiosis.
Option (c) also gives the correct sequence of event but it misses step II (nuclear membrane disassembly). Hence, is ruled out as best appropriate answer is option (a).

Q.10. Anaphase Promoting Complex (APC) is a protein degradaiton machinery necessary for proper mitosis of animal cell. If APC is defective in a human cell, which of the following is expected to occure? (2017)
(a) Chromosomes will be fragmented.
(b) Chromosomes will not segregate.
(c) Recombination of chromosome arms will occur.
(d) Chromosomes will not condense.
During anaphase in mitosis, sister chromatids segregate at opposite poles. Therefore, a defective APC will affect chromosome segregation.

Q.11. During cell growth, DNA synthesis takes place on (2016)
(a) S - phase
(b) G1 - phase
(c) G2 - phase
(d) M - phase
In S-phase (synthetic phase) of cell cycle, the chromosomes replicate. For this their DNA molecules function as templates and form carbon copies. The DNA content doules i.e., 1C to 2C for haploid cells and 2C to 4C for diploid cells. As a result duplicate sets of genes are formed. Along with replication of DNA new chromatin fibres are formed which, however, remain attached in pairs and the number of chromosomes does not increase. As chromatin fibres are elongated chromosomes, each chromosome comes to have two chromatin threads or sister chromatids which remain attached at a common point called centromere.

Q.12. When cell has stalled DNA replication fork, which checkpoint should be redominantly activated? (2016)
(a) G1/S
(b) G2/M
(c) M
(d) Both G2/M and M
If cell has stalled DNA replication fork, it implies that it has crossed CG1 or G1 cyclin cell cycle check point and has entered S-phase of cell cycle, where it is preparing for chromosome replication. Afterwards it will enter G2 phase and will soon approach second check point called mitotic cyclin (CM) which lies between G2 and M-phase).

Q.13. Match the stages of meiosis in column I to their characteristic features in column II and select the correct option using the codes given below. (2016)

The cell cycle

Stages of cell division in a garlic root

(counts from a "root tip squash")
Stage Number of cells
Interphase 872
Prophase 74
Metaphase 18
Anaphase 10
Telophase 8

These numbers can be used to estimate the time taken in the various stages, and to calculate the mitotic index: the ratio of the number of cells undergoing mitosis to the number of cells not undergoing mitosis (i.e. in interphase).

Within the cell cycle, mitosis is the name given to nuclear division, and it consists of a number of phases: prophase, prometaphase, metaphase, anaphase and telophase.

Cytokinesis (division of the cytoplasm) is normally next, resulting in two cells.

Each of the cells produced after mitosis is genetically identical.

Practical work observing stages of mitosis

  • the preparation of stained squashes of cells from plant root tips
  • set-up and use of an optical microscope to identify the stages of mitosis in these stained squashes
  • calculation of a mitotic index
  • measurement of the apparent size of cells in the root tip
  • calculation of their actual size using the formula: Actual size = size of image / magnification

The microtubule-organizing center (MTOC)

[Another type of MTOC: the basal bodies associated with cilia and flagella].
In animal cells, the MTOC associated with spindle formation is the centrosome, which consists of 2 centrioles.

Proteins involved in the spindlle

Image of the mitotic spindle in a human cell showing microtubules in green, chromosomes (DNA) in blue, and kinetochores in red.
From Wikimedia Commons, the free media repository

Microtubules are composed of tubulin, which is built up from &alpha and &beta sub-units to form hollow tubules.

Within the cell, astral filaments radiate from the MTOC towards the cell membrane at each pole of the cell. Other filaments move into the centre of the cell. K-fibres radiate from the kinetochores which spread our sideways from the centromere regions of the chromosomes.

Each tubule has a polarity ('plus' and 'minus' ends), and subunits are added to one end of the microtubule. Other motor proteins powered by ATP move along the microtubules causing movement in one direction or another.

Kinesins move in a walking action, usually towards the positive end of a microtubule.

Dyneins are motor proteins that move along microtubules, towards the minus-end.

Cytokinesis involves actin and myosin

Lecture 12: Genetics 1—Cell Division and Segregating Genetic Material

In this first lecture on genetics, Professor Martin talks about how information flows between cells, such as from parent cells to daughter cells. He also talks about information flows from one generation to the next, ending lecture with a demo.

Instructor: Adam Martin

Lecture 1: Welcome Introdu.

Lecture 2: Chemical Bonding.

Lecture 3: Structures of Am.

Lecture 4: Enzymes and Meta.

Lecture 5: Carbohydrates an.

Lecture 9: Chromatin Remode.

Lecture 11:Cells, The Simpl.

Lecture 16: Recombinant DNA.

Lecture 17: Genomes and DNA.

Lecture 18: SNPs and Human .

Lecture 19: Cell Traffickin.

Lecture 20: Cell Signaling .

Lecture 21: Cell Signaling .

Lecture 22: Neurons, Action.

Lecture 23: Cell Cycle and .

Lecture 24: Stem Cells, Apo.

Lecture 27: Visualizing Lif.

Lecture 28: Visualizing Lif.

Lecture 29: Cell Imaging Te.

Lecture 32: Infectious Dise.

Lecture 33: Bacteria and An.

Lecture 34: Viruses and Ant.

Lecture 35: Reproductive Cl.

ADAM MARTIN: Well, first of all, nice job on the exam. We were quite pleased with how you guys did. And so from now on in the course, Professor Imperiali has been telling you about information flow, but information flow within itself, so information flow from the DNA to the proteins that are made in the cell, which determines what that cell does. And so we're going to switch directions today. And we're going to start talking about how information flows between cells-- so from a parent cell to its daughter cells. And we're also going to talk about how information flows from generation to the next.

And this, of course, is the study of genetics. And what genetics is as a discipline is it is the study of genes and their inheritance. And the genes that you inherit influences what is known as your phenotype. And what phenotype is is simply the set of traits that define you. So you can think of it as a set of observable traits.

And this involves your genes, as you probably know. I mean, just this morning, I was dropping my son off at school, and he was comparing how tall he was compared to his classmates. And as he went in, he was like, thanks for the genes, dad. So I expect that many of you are going to be familiar with much of what we'll discuss, but we're going to lay a real solid foundation, because it's really fundamental for understanding the rules of inheritance and how that works.

So genetics is the study of genes. So what is a gene? You can think about genes in different ways. And what we've been talking about up until now, we've been talking about molecular biology and what is known as the central dogma. And the central dogma states that the source of the code is in the DNA. And there's an information flow from a piece of DNA, which is a gene. And the gene is a piece of DNA that then encodes some sort of RNA, such as a messenger RNA. And many of these RNAs can make specific proteins that do things in your cells in your body. So that's one very molecular picture of a gene.

You can think of a gene as a string of nucleotides. And there might be a reading frame in those nucleotides that encodes a protein. So that's a very molecular picture of a gene. The field of genetics started well before we knew about DNA, and its importance, and what the DNA encoded RNA which encoded proteins. So the concept of a gene is much older than that.

And so another way you can think of a gene is it's essentially the functional unit of heredity. So it's the functional unit of heredity. I'll bump this up. So I want to just briefly pause and kind of give you an overview of why I think genetics is so important.

So what you saw up here is you saw a cell divide. And I showed you this in the last lecture-- you saw the chromosomes, which are here, how they're segregated to different daughters. And this is-- basically, you're seeing the information flow from the parent cell into the daughter herself. But we saw this, so I'm just going to skip ahead.

So why is this so important? I'm going to give you a fairly grandiose view of why genetics is so important. And I'm going to say that we can make a good argument that genetics is responsible for the rise of modern civilization. Humans, as a species, began manipulating genes and genetics even before we had any understanding of what was going on. So this is more of an unconscious selection.

And so 10,000 years ago, humans were hunter gatherers. They'd go out, and try to find nuts and seeds, and hunt animals. And that's how we got our food. But around 10,000 years ago was the first example of where humans, as a species, really altered the phenotype of a plant, in this case. So wild wheat and wild barley, the seeds develop in a pod. And the biology of the wild wheat is such that the pod shatters, and the seeds then spread on the ground where they can then germinate into new plants.

But 10,000 years ago, humans decided that it would be more ideal if we had a form of wheat which didn't shatter, which is known as non-shattering wheat in which the seeds remain on the plant. And that allows it to be easily harvested at the end of the season. So 10,000 years ago is one of the first examples where humans really genetically altered the phenotype of a plant. And they selected for this non-shattering wheat, which then allowed for the rise of agriculture.

In addition to wheat, we also-- about 4,000 years ago was the rise of domesticated fruit and nuts. So here are some almonds. If you would like an almond, feel free to have some. You guys want some almonds? No. If you have a nut allergy, don't eat them. Great.

So wild almonds, when you chew them, there's an enzymatic reaction that results in cyanide forming. Rachel just stopped chewing. Don't worry. These are almonds that are harvested at Trader Joe's, so you're safe. And so the wild almonds, obviously, were not compatible for consumption. But 4,000 years ago, humans again selected for a form of the almond, which involved just a single gene, which was non-bitter and known as a sweet almond, which was also not toxic.

So this doesn't just go for foods, but also for clothing. So humans have selected for cotton with long lint. And that served as a basis for clothing and sort of allowing us to have fabric. And I just want to end with a little story about the almond, which is part of the archaeological evidence for when almonds were domesticated was when King Tut's tomb was unearthed. And they found a pile of almonds next to the tomb, because the Egyptian culture, what they did is they buried the dead with food to sustain them in the afterlife. So that just gives you an idea as to how far back the importance of genetics goes.

If we think about nowadays, right now you are always seeing genetics in the news. And you also have the opportunity yourself to sort of do your own genetic experiment. And so now you guys are undoubtedly aware of all these companies that want you to send them your DNA. And they also want you to send them money, such that they can give you information about your family tree and also information about your health.

So this is now a big business. But if you don't understand genetics, this is not as useful as it could be. So I'm just curious. How many people here have used one of these services and had their DNA genotyped? Cool. And do you think that really changed your view of who you are? Or was it kind of, eh?

AUDIENCE: We actually-- I don't know if we even looked at where we came from. We looked for genetic disease.

ADAM MARTIN: So you're looking for genetic disorders. And you don't have to tell me anything about that. Yeah, so I have not done this, but my dad has done it. And he will go find his relatives and bore them with our ancestry. So this is one example of how genetics is really in play today. And not everyone knows how this works. I've had people at Starbucks in the morning come up to me with their 23andMe profile and ask me to explain stuff, because they know who I am. It's a little awkward.

So we can also use genetics for forensics. And so this is kind of a-- I had a lab manager in the lab, and he told me that people were doing this in senior homes in Florida, which I thought was kind of funny. What I find hilarious about this is the mug shot of the dog. That dog looks so guilty. But you can use DNA to-- you can use DNA to genotype poop. You can genotype your neighbor's dog. You can get evidence that they're the one that's pooping on your lawn. So that's a not-so-serious example.

But there are more serious examples of where DNA genotyping is really having an effect in our society. And this is something I mentioned in the intro lecture. Just this past spring, someone was suspected as being the Golden State Killer. This is a cold case. The killings happened 40 years ago, but the break came from investigators getting DNA from the suspect's relatives to implicate this person in this crime. So they had DNA from the crime. And they saw that there were matches to the DNA at the crime to certain people. And then they can reconstruct who might be the person in the right place to commit the crime.

So this is-- I think this is interesting, because it also leads to all sorts of privacy issues, right? Who's going to gain access to your genotype if you submitted to these companies, right? I mean, this is probably a case where I'd argue there's probably a beneficial result in that you can actually figure out if someone's committed a crime. But there are other issues in terms of thinking about insurance companies where we might be interested in having our information not publicly available to insurance companies. And maybe this is something we can discuss later on in another lecture.

For today, I want to move on and go through really the fundamentals of genetics. And what I'm going to do is I'm going to start with the answer. OK? I'm going to present to you guys today the physical model for how inheritance happens. OK? So today, we're going to go over the physical model of inheritance.

And this physical model involves cell division, which you saw in the last lecture and also in my opening slide. It involves cell division and the physical segregation of the chromosomes during cell division. So also chromosome segregation.

OK, so this is how I'm going to represent chromosomes. And I just want to step you through what it all means. So I have these two arms that are attached to this central circle. The circle is meant to represent the centromere. So this is the centromere.

And you'll remember from the last lecture on Monday, the centromere is the piece of the chromosome that physically is attached to the microtubules that are going to pull the chromosomes to separate poles. OK? So that's called the centromere. And usually, it's denoted, it's like a constriction in the chromosome or a little circle. OK?

These other parts of the chromosome are the chromosome. So that you have the arms of the chromosome. Now I'm drawing what's known as a metacentric chromosome. It's not important that you know that term. But it just means that the centromere is in the middle of the chromosome. There are other types of chromosomes with the centromere might be at the end. OK? So there are different types of chromosomes.

All right, now, for all of us, we have cells that have different numbers of chromosomes. OK? Some of our cells are what is known as haploid. And what I mean by haploid is there is a single set of chromosomes. Now the cells that we have that are haploid are our gametes, so they're our eggs and our sperm cells. OK? So these include gametes.

OK, but most of the cells in your body are what is known as diploid. And diploid means there's two complete sets of chromosomes. OK, and you get one set from one parent, the other set from the other parent. OK? So one set from each parent.

OK, and I'll draw the other set like this. And what I'll do is I'll just shade in this one to denote that it's different. OK? So these two chromosomes then are what is known as homologous. They're homologous chromosomes. Homologous.

OK, and what I mean by them being homologous is that, basically, these two chromosomes have the same set of genes. OK, so they have the same genes. They have the same genes. But they have different variants of those genes. OK, so different variants of these genes. And these variants are referred to as alleles. OK? So if you have the same gene but they differ slightly in their nucleic acid sequence, then they're distinct alleles of those genes.

So often, the way geneticists refer to these different variants or alleles is we use a capital letter and a lower case letter. OK, so this chromosome over here might have a gene that's allele capital a. And then this homologous chromosome will have the same gene but a different allele, which I'll denote lowercase a. OK?

So in this case, big A and little a are different alleles of the same gene. They might produce a slightly different protein, which would result possibly in a different phenotype. OK? So everyone understand that distinction?

Oh, I want to make one point because this came up last semester and was one of those cases where I forgot the part about the head. So we often just have two alleles when we teach genetics. But I hope you can see that because a gene is a long sequence of DNA, there is a ton of different alleles you can have within a given gene. So one nucleotide difference in that gene would result in a different allele. OK? So we often refer to two alleles, but there can be more than two alleles for a given gene. OK? Does everyone see how that manifests itself? OK, great. Any questions up until now? Yes, Carmen?

AUDIENCE: So when you say that there's more than one, more than just the two alleles, I don't have more than one on each chromosome. So they're just more than one--

ADAM MARTIN: In the population. So Carmen asked, well, can I have like five alleles of a gene? And that's a great question. And so thank you, Carmen, for asking that. What I mean is if we consider a population as a whole, right?

You have two alleles of each gene, unless it's a gene that somehow duplicated. And so when we're considering the population, there can be more than-- right? I mean, I see we have people with-- hair color is not a monogenic trait. But we have people with black hair, with blond hair, with brown hair, right? There is more than just two possible alleles with possible phenotypes. OK?

All right, let's go up with this. All right, now I want to start at the beginning. So most of our cells are diploid. And the origin of our first diploid cell is from the union of two gametes. OK? So I'm going to draw two gametes here. Each is one n.

And I'm just going to draw one set of chromosomes for this here. So we might have a male gamete and a female gamete. And what I'm referring to when I say n here, n is basically referring to the number of chromosomes per haploid genome. So when you have one n, it means you're haploid because you have only one set of haploid genome.

But early in your life, we're all the result of a fusion between a male and female gamete. And so that creates a diploid cell. OK, so now, this diploid zygote, so this is referred to as the zygote, is diploid and now has a set of homologous chromosomes. OK? So I'm only drawing one set of homologous chromosomes here.

So on the board, I'm going to stick to just one, so I don't have to draw them all out. In the slides, I have three. OK? So each of these represents a chromosome. These are different chromosomes. Different chromosomes are either different color or have a different centromere position. And then these down here that are colored are going to be the homologous chromosomes. OK? Do you see how I'm representing this?

OK, so once you have the zygote, right, so you guys are no longer one cell, right? You guys each are tens of trillions of cells. So this zygote cell had to reproduce itself, and your cells had to divide, so that you grew into an entire multicellular organism. I'll just quickly erase that.

OK, so when most of your cells divide, and most of your cells are known as somatic cells. When cells of your body or your intestine and your skin, when they divide, they genetically replicate themselves. And they're undergoing a type of cell division known as mitosis. OK?

In mitosis, it's essentially a cloning of a cell. Or ideally, it's the cloning of a cell. So you have a diploid cell. It has to undergo DNA replication . And when a chromosome undergoes DNA replication, it will, during mitosis look like this. OK?

And these two different arms or strands, they're known as sister chromatids. OK? So that's just another term you should know. These are sister chromatids. OK, and the sister chromatids, if DNA replication happens without any errors, should be exactly the same as each other in terms of nucleotide sequence. OK?

So after DNA replication, this cell will essentially have four times the amount of DNA as a haploid cell. And it will split into two cells. And again, they'll both be diploid. OK? And I'll just point out, if we're thinking about our pair of chromosomes here, right, this parent cell has both homologs. And the daughter cells, because they should be genetically identical, also have both homologs.

OK, so that's an example with just one chromosome. I'll take you through an example with these three chromosomes here-- all six chromosomes. So you have-- these are homologs. These are homologs. These are homologs. And during mitosis, all of these chromosomes initially are all over the nucleus.

But during mitosis, they will align along the equator of the cell and what is known as the metaphase plate. Metaphase is just a fancy term for one particular stage in the mitotic cycle. And then what will happen is the spindle will attach to either one side or the other side of these chromosomes.

And it will physically segregate them into different cells, OK? And what I hope you see here is that this has six chromosomes. This has six chromosomes. And these two daughter cells are genetically identical to the parent cell. OK, so this is known as an equational division, because it's totally equal. OK?

And again, the daughter cells are both diploid, OK? So that's mitosis. Any questions about mitosis? OK. Moving on, we're going to talk now about another type of cell. And these are your germ cells. And these germ cells undergo an alternative form of cell division known as meiosis, OK? And your germ cells-- germ cells produce your egg and sperm.

And so meiosis essentially is producing gametes, such as egg and sperm cells, OK? So what's the final product going to be? What should be the genomic content of the final product of meiosis? It should be one end, right? Who said that? Sorry. Yeah, exactly right. What's your name?

ADAM MARTIN: Jeremy. So Jeremy is exactly right. Right? The germ cells-- in order to reproduce sexually, they should be haploid cells, so that they can combine with another haploid to give rise to a diploid, OK? So the ultimate result that we want is to have cells that are one end.

But most of our cells to start out with are diploid, so they're two end, OK? So what's special about meiosis is you're not just going from two end to two end, but you're reducing the genetic content of the cells. You're going from two end to a one end content, OK?

So again, meiosis starts with DNA replication. But in this case, the first division, which is meiosis I, is not equal. And it actually segregates the homologs, such that you get one cell that has one of the homologs duplicated and another cell that has the other homolog duplicated. OK?

And I'll show this. I'll show it right now. So this is the same cell now. It's undergone DNA replication. As you can see, each chromosome has two copies. But instead of all the chromosomes lining up in the same position of the metaphase plate, what you see is that homologous chromosomes pair at the metaphase plate.

And what happens here is that the homologous chromosomes are separated-- two different cells. And now, you have two cells that are not genetically identical, OK? So because there is not equational and there's a reduction in the genetic material that's present in the cells, this is known as a reductional division, OK?

So that's meiosis I. And that's a reductional division. And then-- but this is not yet haploid. And so-- here, I'll just stick another one in here. These cells then undergo another round of division, which is known as meiosis II. And during this meiosis, these sister chromatids are separated, such that you're left with one chromosome.

And my drawing-- at least one chromosome per gamete, OK? So each of these, then, is 1n. OK? So again, you have the chromosomes. But this time, you have them aligned like in mitosis. They align. The sister chromatids are physically separated.

And now, you see this cell is genetically identical to this cell. And this cell here is genetically identical to this cell, OK? So that's meiosis II. And that's an equational division much more like mitosis, OK? Because the product of the division of those two cells-- each of those is equal, OK?

And finally, the result of meiosis II is that you're then left with gametes that have a haploid content of their genome. OK, I want to end lecture by doing a demonstration. Let's see. So this could either be amazing, or it will be a complete disaster. So we're totally going to do it. So everyone come up. Right here. Here.

Evelyn, you can leave when you have to go. And we'll have a chromosome loss event. OK? It has to be a multiple of four. If we have extra people label, then the people can supervise. Go. Oops, sorry. All right. What do we got here? Here you go, Bret, Andrew. Sorry. I hope I'm not hitting anybody.

ADAM MARTIN: What's that? Yeah, that's the advantage of these. All right. Here you go, Myles. Let's see. Here you go. Sorry. Someone take this. All right. What do we got here? Just got a little chromosome here.

ADAM MARTIN: Oops, sorry. All right. Who doesn't have a chromosome? Everyone in the class has a chromosome? All right. One of you want to come in here? All right. We'll see how constrained we are in terms of space.

I've never been this ambitious and had this many chromosomes before, so I'm excited to see how this works. So you each have a Swim Noodle. They're different colors, so different colors represent different chromosomes. And then you also have Swim Noodles that have tape on them.

And these represent different alleles from your other chromosomes. So these two chromosomes would be homologs of each other, OK? Does that make sense? OK, great. All right. Now, the metaphase plate will be along the center of the room.

So let's first reenact mitosis. So why don't you guys find your sister chromatid and then sort of align in the middle of the room here? Sister or brother chromatid. How are we doing? Do we have enough space there? It's a little packed. You can see how the cell-- can you imagine how packed it is inside a cell?

OK, everyone found their sister chromatid. Normally, the sister chromatids-- they replicate and they get held together. So there's no finding of sister chromatids, but-- all right. Great. So segregate and we'll see how you guys did. All right. And the goal is that you guys would be genetically identical. So how-- OK, great.

That looks like one short red, one short red. OK, that's good. They look genetically identical to me. All right. So that was my mitosis. Now, we're going to do meiosis. OK, why don't you guys align, like what would happen during meiosis I. OK, you guys can come back. Think about who you're going to pair with.

All right. So what were you looking for when you were pairing? Who were you looking for?

AUDIENCE: Longest chromosome.

ADAM MARTIN: Your longest chromosome, right? OK, great. All right. Why don't you guys segregate? All right, so that was meiosis I. Meiosis I looks successful to me. And now, we have to undergo meiosis II. So maybe what we could do is you guys can rotate. And the metaphase spindle can be sort of in this orientation.

ADAM MARTIN: Yeah, that will-- we want a group over there, a group over there, a group here, a group here. And those will be our four gametes.

All right. You guys set? All right. Go.

OK, terrific. Everyone haploid? Looks like everyone is haploid, which is good. Right? So let's just take a minute and think about probability here. So what was the probability that a gamete would end up with this orange allele on the red chromosome?

ADAM MARTIN: Half, right? Because there are two, right? So these two gametes have that allele. These two should not, right? OK, great. And we just had a chromosome loss, so that gamete is in trouble. But maybe we could get a TA to rescue this chromosome. Either one of you is fine. There you go, David.

All right. That was great. Now, let's-- as you're doing this, you get a sense as to how things could get mixed up, right? And you think inside the cell, right? So I don't-- I've lost track of how many chromosomes. We have 1, 2, 3, 4, 5, 6, right? How many chromosomes do we have?

ADAM MARTIN: We are-- a haploid set for us is how many chromosomes?

ADAM MARTIN: 23. Exactly. Right? So it'd be even worse for a human cell to get this to go right. So why don't you guys line up in the mitosis configuration? And we'll consider some things that could go wrong. All right. Who here is good friends with their sister or brother chromatid? Is anyone very good friends with their sister or brother chromatid?

ADAM MARTIN: Yeah. Someone become good friends and become inseparable, OK? Would someone volunteer to be inseparable? OK, great. You guys are now inseparable, OK? Now, segregate. OK, great. Now, what happened there?

ADAM MARTIN: Yeah, that's cell stole her. OK. So now, we have two-- a duplication of that chromosome. What's happened over here with this daughter cell?

AUDIENCE: It's missing a chromosome.

ADAM MARTIN: It's missing a chromosome, right?

ADAM MARTIN: So these are the types of mistakes that can be associated with a cell becoming cancerous, right? Because let's say there was a gene that suppresses growth on that chromosome. And it wasn't on that homolog. Then you might result in a genetic sort of mutant or loss of that gene that would result in uncontrolled proliferation.

Also, picking up the extra copies of genes that promote growth could allow that cell to have a proliferative advantage, OK? We're going to-- this is sort of foreshadowing what we're going to talk about later. But I just want to plant the seed now. OK. Why don't we go back and do meiosis?

OK. Now, anyone see any friends looking across the aisle now? All right. Great. You guys are now inseparable. Why don't you guys segregate, except the inseparable ones? Oh, but your sister chromatids still have to stay attached. There you go. See? Great. Right. So just like last time, this is known as a non-disjunction event where the chromosomes don't separate when they should, OK? Great. Now, why don't you guys do meiosis II?

All right. You can segregate. All right. Now, you see these two gametes over here are lacking an entire orange chromosome. And these two gametes here have picked up an additional copy of an orange chromosome, OK?

So these two gametes are no longer haploid for the orange chromosome. And if one of these gametes were to fuse with a haploid gamete that has an orange chromosome, then now you have a zygote that has three copies of the orange chromosome, which is abnormal, OK?

So if that were chromosome 21 in humans, that would result in something that's called trisomy 21, which is down syndrome, OK? So you see how mistakes in how chromosomes segregate can result in human disease. OK. Why don't we give yourselves a hand? Good job.

OK, you can just throw the Pool Noodles on the side. And I just have one slide to show you where we're going next. [INAUDIBLE]

AUDIENCE: So I have a question.

AUDIENCE: When the homologous chromosomes split, can you share alleles? Are there alleles preserved in this portion?

ADAM MARTIN: You're asking if there's crossing over?

ADAM MARTIN: There is crossing over. Yes. And that will get its own entire lecture. Yes, good question. OK, so just to give you guys a preview of what's up next. So in the next lecture, we're going to talk about Mendel and Mendel's peas. And we'll talk about the laws of inheritance, OK?

And realize Mendel was way before DNA or what our knowledge of a gene was, OK? Next, we'll talk about fruit flies, and Thomas Hunt Morgan, and seminal work that led to the chromosome model of inheritance and also resulted in the concepts of linkage and also genetic maps.

OK, we're going to go-- well, just to sort of anchor yourself, the structure of DNA was published in 1953. So these seminal genetic studies up here were done before we knew about DNA. So geneticists were studying genes and their behavior well before we knew DNA was what was responsible.

And then we'll talk about sequencing and the sequencing revolution. We'll talk about cloning, and molecular biology, and how one might go from a human disease to a specific gene that causes it. And then, finally, we'll start talking about entire human genome and genome sequences. OK, so that's just a preview of where we're going, so have a great weekend.

Interactive resources for schools

Asexual reproduction

Reproduction not involving the fusion of gametes.

Natural selection

The process in nature where the fittest individuals survive, reproduce and pass their characteristics on to their offspring.


Cell division

The process by which a parent cell divides into two daughter cells


A chromosome is like a packet of coiled up DNA. Humans have 23 pairs of chromosomes. They are in the nucleus of every human cell.

Cell Cycle

Controlled sequence of events that results in cell division in the body cells.


A distinct part of the cell, such as the nucleus, ribosome or mitochondrion, which has structure and function.

Eukaryotic cells

Cells that make up animals, plants, fungi and protista. They are three-dimensional, membrane-bound sacs containing cytoplasm, a nucleus and a range of membrane-bound organelles.


A change in the arrangement or amount of genetic material in a cell.


A theory, supported by much evidence, which suggests that the animal and plant species inhabiting the earth today are descended from simpler forms by a gradual process of change.


A list of often difficult or specialised words with their definitions.


The type of cell division, which occurs in the ovaries and testes, to produce cells with a haploid number of chromosomes.


The part of a cell that controls the cell function and contains the chromosomes.


Reusable protein molecules which act as biological catalysts, changing the rate of chemical reactions in the body without being affected themselves


The sex cells (ova and sperm) that join together to form a new unique diploid cell in sexual reproduction.


Division of a cell nucleus which results in each daughter cell having the same number of chromosomes as the parent cell.


A mass of abnormal cells which keep multiplying in an uncontrolled way.

The basic unit from which all living organisms are built up, consisting of a cell membrane surrounding cytoplasm and a nucleus.

Deoxyribonucleic acid. This is the molecule which contains the genetic code. It coils up tightly inside chromosomes. DNA is a double helix made from two strands which are joined together by pairs of bases.

Cell division – key process in growth, repair and reproduction

Inside your body, around 1 billion cells die every hour. In this time a similar number are made. The ability of cells to divide and make new cells is vital for life. In eukaryotic organisms, mitosis results in two daughter cells with identical copies of the parent cell DNA. Meiosis results in daughter cells with half the number of chromosomes of the parent cell. This is the type of cell division needed for sexual reproduction..


Why is cell division so important?

Whenever multicellular organisms grow, more cells are required. New cells are also needed all the time to replace those that wear out, or become damaged or destroyed. Mitosis is the key process here. The rate of mitosis varies greatly, depending on many factors including the life stage of an organism and the type of cells involved.

Enzymes control cell reactions whatever the organism and wherever it is growing

The rate of mitosis is controlled within the cell cycle. This is a sequence of events including the replication of the DNA and the cell organelles prior to cell division, the division of the nucleus and the subsequent division of the cytoplasm with all its contents. If control of the cell cycle is lost, tumours and cancer may result.

All organisms need to reproduce. Many organisms produce identical offspring by asexual reproduction, and for that they need mitosis. Some organisms reproduce sexually, with gametes combining to produce a unique new individual containing genetic information from both parents. The formation of gametes depends on meiosis.

Mutations can arise during mitosis and meiosis. Mutations during mitosis often cause problems for the organism including cancer formation. Mutations during meiosis drive natural selection and evolution, but can also result in genetic diseases.

The cell cycle – key to health and disease

Photos by Anthony Short unless credited otherwise. Animations and diagrams by Edward Fullick throughout.

Cell Biology Report

I have produced this illustrated report to demonstrate the basic principles of life and cells. I will show that I understand basic cell structure by:  Discussing the selected characteristics of living cells.  Comparing and contrasting prokaryotic and eukaryotic cells and explaining the impact viruses have on them.  Discussing eukaryotic sub-cellular structure and organelles. I will then go onto show my understanding of cellular metabolism by explaining:  The role of the cell membrane in regulating how nutrients gained and, waste products lost.  How animal cells use nutrients to provide the energy for growth, movement, and cell division.  The role of nucleic acids in the nucleus and cytoplasm.  Discussing the synthesis of proteins. Finally, I will show that I understand how cells grow and divide by explaining:  The generation of specialised tissues from embryonic stem cells.  The process of interphase and factors that initiate cell division and their importance.  How the same genetic information received by each daughter cell.  Comparing and contrasting cancer cells with normal cells.

The research I have undertaken has consisted of study materials provided by LearnDirect, reading and gathering information, images, diagrams and tables from educational platforms and online articles, enabling me to present my understanding of cell biology in this illustrated report.

Cell Structure

Selected characteristics of living cells

Cells are the basic unit of life. Every living organism contains cells. Living organisms have these seven characteristics in common:

‘Movement - they can move and change their position. Reproduction – they can make more of the same kind of organism as themselves. Sensitivity – they can detect or sense stimuli and respond to them. Growth - they can permanently increase their size or dry mass by increasing the number or size of their cells. Respiration – they can create chemical reactions that break down nutrient molecules in living cells to release energy. Excretion – they can excrete toxic materials, waste products of metabolism, and excess substances. Nutrition - they can take in and absorb nutrients such as organic substances and mineral ions. These nutrients contain the raw materials or energy needed for growth and tissue repair.’ (, BBC Bitesize – Revision, 2020)

MRS GREN – using this acronym is a great way of remembering the characteristics.

Prokaryotic and Eukaryotic Cells

There are two basic types of cells, prokaryotic cells (bacteria and archaea) and eukaryotic cells (animals, plants, fungi and protists). Both prokaryotic and eukaryotic cells have structures in common. All cells have a cell membrane, ribosomes, cytoplasm and DNA.

Figure 1 – Prokaryotic cell and Eukaryotic cell (, 2020)

By definition, prokaryotic cells are single-celled organisms and do not have a true nucleus or membrane-bound organelles. In contrast, eukaryotic cells have a more intricate structure than prokaryotic cells and contain membrane-bound organelles. A eukaryotic cell is approximately ten times larger in diameter than a prokaryotic cell.

Viruses and their impact on cells

‘A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism.’ (Wikipedia, 2020)

Figure 2 – Virus structure (, 2020)

Viruses are non-living particles which depend on host cells they infect to reproduce. The host cells normal functions are hijacked by the virus and, produce more viral protein and genetic material instead of their usual products. There are six key stages in the virus replication cycle attachment, penetration, uncoating, replication, assembly, and release.

The effect viruses have on prokaryotic and eukaryotic cells is different because these cells structures are divergent.

Viruses cause several viral diseases in eukaryotic cells, a few examples of these would be AIDS, the common cold, chickenpox and influenza. The virus has receptors for the cells to attach too. It can then enter and replicate its genetic material in the nucleus, taking control of the cell's metabolism. Before the infection is fully-fledged, the virus has to afflict through many cells.

Bacteriophages are viruses that infect and replicate within prokaryotes. They have a lytic cycle (leads to death of host cell) or lysogenic cycle (leads to the integration of phage into the host genome).

Cellular metabolism

The role of the cell membrane

Figure 5 – Cell membrane (, 2020)

All living cells need nutrients to be able to sustain life. The cell membrane controls what substances go in and out of the cell. The basic structure of the cell membrane is made up of:  Phospholipids  Proteins  Carbohydrates

How substances move across the cell membrane

How substances cross the cell membrane depends on the nature of the substance. Below are the different possible methods:

Lipid diffusion Figure 6 – Lipid diffusion (, 2020)

Used for transportation of lipid soluble molecules (water, oxygen, steroids and carbon dioxide). Diffusion occurs in the lipid bilayer, this is where substances move down gradients of concentration levels (no energy is needed to do this).

Figure 7 – Osmosis (, 2020)

Diffusion of water molecules across the membrane, from a region of higher to lower concentration. There are 3 types of solutions:

  1. Isotonic – concentration is the same as the cell (no water enters or exits).
  2. Hypertonic – concentration is

higher than the cell (water molecules exit). 3. Hypotonic – concentration is lower than the cell (water molecules enter).

Facilitated diffusion Figure 8 – Facilitated diffusion (Hughes, 2.1)

Uses trans-membrane proteins to help molecules cross the membrane. The transport protein molecules are found in two different forms:

  1. ‘Channel proteins which form a pore or channel in the membrane. It is usually charged substances such as ions which make use of these proteins. The channels are often gated to allow the cells to control the entry or exit of these ions.
  2. Carrier proteins which have binding sites for specific solutes, such as glucose. They can flip between two states so that the site is alternately open to opposite sides of the membrane. A substance which is to be transported binds on the side where it is more concentrated and released where it is less concentrated.’ (Hughes, 2.1)

Active transport Figure 9 - Active transport (Hughes, 2.1)

Uses a trans-membrane protein (pump-molecule) to transport substances from a region of lower to higher concentration gradient.

Cell division requires movement of key structures within the cell. There are two types of cell division in animal cells, these are mitosis – process of making new cells and meiosis – cell division that creates egg and sperm cells. These processes happen within the nucleus.

Figure 12 – Cell division (, 2020)

Nucleic acids

Nucleic acids are macromolecules. They’re chains of nucleotide which provide genetic information. ‘A nucleotide is made up of three parts: a phosphate group, a 5-carbon sugar, and a nitrogenous base.’ (, 2020) In DNA there are 4 nitrogenous bases: adenine, cytosine, guanine and thymine. Instead of thymine, RNA contains uracil. Nucleotides combined form a polynucleotide, DNA or RNA.

Figure 13 – Polynucleotide strands with DNA and RNA molecules (Hughes, 2.4)

DNA is a double stranded polymer of nucleotides which is situated in the nucleus. RNA is a single stranded polymer of nucleotides which is situated in the cytoplasm. There are 3 forms of RNA, see picture below:

Figure 14 – Different types of RNA molecule (, 2020)

Synthesis of proteins

Proteins, defined as organic macromolecules, are extremely important for growth and repair in eukaryotic cells. A protein structure described in levels, see picture below:

Figure 15 – Structure of a protein shown in levels (Hughes, 2.3)

Different chemical bonds hold the whole molecule together.

Cell growth and division

Specialised tissues from stem cells

By definition, a stem cell is an undifferentiated cell capable of giving rise to indefinitely more cells of the same type and other cells can arise from it by differentiation. (Hughes, 3.1) There are three types of stem cells:  Embryonic – derive from embryos (able to become any other type off cell in the body).  Foetal – found in the tissues of developing foetus.  Adult stem cells – found in the tissues of adults, for example: bone marrow (used to treat blood diseases and blood cancer.

Embryonic stem cells are pluripotent. They evolve from a fertilised egg (zygote), which later develops into the blastocyst. The blastocyst has an inner mass of cells (embryoblast) which become the embryo and an otter mass off cells (trophoblast) which becomes the placenta. Usually, embryos used are ones that haven’t been used in IVF treatment clinics.

Figure 17 – Pluripotent stem cell (

In controlled environments, the stem cells are allowed to divide and multiply. ‘The next step in the process is to actually collect healthy, dividing and undifferentiated cells, which is known as a stem cell line.’ (Hughes, 3.1)

Stem cells have the ability to treat diseases such as, heart disease, cancer and Parkinson’s disease.

Interphase and factors that initiate cell division

Interphase is what a cell goes through when it divides, it is a part of the cell cycle.

Figure 18 – Cell cycle (, 2020)

Interphase has different phases: G1 (the cell grows), S (synthesis of new DNA), and G (prepares for mitosis).

Mitosis is broken down into 4 stages: prophase, metaphase, anaphase and telophase. See diagram below: Figure 19 – Summary of mitosis and it’s different stages (Hughes, 3.3)


The cell is a complex living organism. Each and every organism is made up of equally complex microorganisms. They work in harmony to sustain life. Without intervention, cells grow, metabolise and divide. Cells are the smallest structural and functional unit of life. It is important cells are kept healthy in order for them to go through their routine functions efficiently.

Cell biology allows us to be able to understand life, which has enabled us to find ways to preserve and create life with science and medicine. The study of cells has led to the treatment of many diseases, illnesses and fix issues with fertility.


To begin with all the terminology was a bit beyond me, but I soon found by writing things down and what they mean my confidence grew as I was able to refer back to my ‘help sheet’ for clarity.

In the future I will use more videos when researching as they are more easy to follow. I also need to allow more time for researching and revising.


Much emphasis has been put on Cdc2 Tyr phosphorylation as the regulatory mechanism that ensures the coordination between cell growth and cell division. However, the fact that a synthetic CDK lacking the regulatory phosphorylation site still exhibits a significant degree of cell size homeostasis [18] argues strongly for the existence of other layers of regulation. Furthermore, we have shown here regulation of mitotic onset without involving CDK Tyr15 phosphorylation. Our work has identified new components of characterized pathways and has revealed the existence of new regulatory mechanisms, and therefore provides a more complete view of the regulatory network of G2/M control.

The invader

“Know your enemy,” Sun Tzu, the great sage of war, wrote some 2,500 years ago. Today, as COVID-19 spreads around the globe, the greatest army of medical scientists ever assembled is bent on learning all it can, as fast as it can, about SARS-CoV-2, the virus behind the pandemic.

Here’s a primer on viruses in general and SARS-CoV-2 in particular. As researchers learn more and more about the novel coronavirus that causes COVID-19, this knowledge — gathered through unmatched levels of scientific cooperation — is being turned against the virus in real time.

Not that this will be a simple pursuit. Compared with a lab dish, living people are complicated. The cells in that dish aren’t the same as the cells in living tissues affected by SARS-CoV-2. Plus, the environment surrounding, say, a lung cell in a person’s body is different from the one in a culture dish. And then there’s this thing called “side effects.” You don’t see those in a dish. But you may in a COVID-19 patient.

Illustration by Jeffrey Decoster

What, exactly, is a virus, anyway?

Viruses are easily the most abundant life form on Earth, if you accept the proposition that they’re alive. Try multiplying a billion by a billion, then multiplying that by 10 trillion. That — 10 to the 31st power — is the mind-numbing estimate of how many individual viral particles populate the planet.

Is a virus a living thing? Maybe. Sometimes. It depends on location. “Outside of a cell, a viral particle is inert,” virologist Jan Carette, PhD, associate professor of microbiology and immunology, told me. On its own, it can’t reproduce itself or, for that matter, produce anything at all. It’s the ultimate parasite.

Or, you could say more charitably, it’s very efficient. Viruses travel light, packing only the baggage they absolutely need to hack into a cell, commandeer its molecular machinery, multiply and make an escape.

There are exceptions to nearly every rule, but viruses do have things in common, said Carette.

A virus’s travel kit always includes its genome — its collection of genes, that is — and a surrounding protein shell, or capsid, which keeps the viral genome safe, helps the virus latch onto cells and climb inside, and, on occasion, abets a getaway by its offspring. The capsid consists of identical protein subunits whose shapes and properties determine the capsid’s structure and function.

Some viruses also wear greasy overcoats, called envelopes, made from stolen shreds of the membranes of the last cell they infected. Coronaviruses have envelopes, as do influenza and hepatitis C viruses, herpesviruses and HIV. Rhinoviruses, which are responsible for most common colds, and polioviruses don’t.

Enveloped viruses particularly despise soap because it disrupts greasy membranes. Soap and water are to these viruses what exhaling garlic is to a vampire, which is why washing your hands works wonders.

How do viruses enter cells, replicate and head for the exits?

For a virus to spread, it must first find a way into a cell. But, said Carette, “penetrating a cell’s perimeter isn’t easy.” The outer membranes of cells are normally tough to get into without some kind of special pass. Viruses have ways of tricking cells into letting them in, though.

Typically, a portion of the virus’s cloak will have a strong affinity to bind with one or another protein that dots the surfaces of one or another cell type. The binding of the virus with that cell-surface protein serves as an admission ticket, easing the virus’s invasion of the cell.

The viral genome, like ours, is an instruction kit for the production of proteins the organism needs. This genome can be made up of either DNA, as is the case with all creatures except for certain viruses, or DNA’s close chemical relative RNA, which is much more flexible and somewhat less stable. SARS-CoV-2’s genome is made of RNA, as are the genomes of most mammal-infecting viruses.

In addition to the gene coding for its capsid protein, every virus needs another gene for its own version of an enzyme known as a polymerase. Inside the cell, viral polymerases generate numerous copies of the invader’s genes, from whose instructions the cell’s obedient molecular assembly line produces capsid subunits and other viral proteins.

Among these can be proteins capable of co-opting the cellular machinery to help viruses replicate and escape, or of tweaking the virus’s own genome — or ours. Depending on the type of virus, the genome can contain as few as two genes — one for the protein from which the capsid is built, the other for the polymerase — or as many as hundreds.

Capsids self-assemble from their subunits, often with help from proteins originally made by the cell for other purposes, but co-opted by the virus. Fresh copies of the viral genome are packaged inside newly made capsids for export.

Often, the virus’s plentiful progeny punish the good deed of the cell that produced them by lysing it — punching holes in its outer membrane, busting out of it and destroying the cell in the process.

But enveloped viruses can escape by an alternative process called budding, whereby they wrap themselves in a piece of membrane from the infected cell and diffuse through the cell’s outer membrane without structurally damaging it. Even then, the cell, having birthed myriad baby viruses, is often left fatally weakened.

Illustration by Jeffrey Decoster

Introducing the coronavirus, and how it latches on

Now we know how your average virus — an essentially inert particle on its own — manages to enter cells, hijack their molecular machinery, make copies of itself and move on out to infect again.

That just scratches the surface. Of the millions of different viral species identified so far, only about 5,000 have been characterized in detail. Viruses come in many shapes and sizes — although they’re all small — and infect everything, including plants and bacteria. None of them works in precisely the same way.

So what about coronaviruses?

Enveloped viruses tend to be less hardy when they’re outside of cells because their envelopes are vulnerable to degradation by heat, humidity and the ultraviolet component of sunlight.

This should be good news for us when it comes to coronaviruses. However, the bad news is that the coronavirus can be quite stable outside of cells because its spikes, protruding like needles from a pincushion, shield it from direct contact, enabling it to survive on surfaces for relatively long periods. (Still, soap or alcohol-based hand sanitizers do a good job of disabling it.)

As mentioned earlier, viruses use proteins that are sitting on cells’ surfaces as docking stations. Coronaviruses’ attachment-enabling counterpart proteins are those same spikes.

But not all coronavirus spikes are alike. Relatively benign coronavirus variants, which at their worst might cause a scratchy throat and sniffles, attach to cells in the upper respiratory tract — the nasal cavities and throat. The viral variant that’s driving today’s pandemic is dangerous because its spike proteins can latch onto cells in the lower respiratory tract — the lung and bronchial cells — as well as cells in the heart, kidney, liver, brain, gut lining, stomach or blood vessels.

Antibody treatments could block binding

In a successful response to SARS-CoV-2 infection, the immune system manufactures a potpourri of specialized proteins called antibodies that glom on to the virus in various places, sometimes blocking its attachment to the cell-surface protein it’s trying to hook onto.

Stanford is participating in a clinical trial, sponsored by the National Institutes of Health, to see if antibody-rich plasma (the cell-free part of blood) from recovered COVID-19 patients (who no longer need these antibodies) can mitigate symptoms in patients with mild illness and prevent its progression from mild to severe.

Monoclonal antibodies are to the antibodies in convalescent plasma what a laser is to an incandescent light bulb. Biotechnologists have learned how to identify antibody variants that excel at clinging to specific spots on SARS-CoV-2’s spike protein, thus thwarting the binding of the virus to our cells — and they can produce just those variants in bulk. Stanford is conducting a clinical trial of a monoclonal antibody for treating COVID-19 patients.

A worry: Viral mutation rates are much higher than bacterial rates, which dwarf those of our sperm and egg cells. RNA viruses, including the coronavirus, mutate even more easily than DNA viruses do: Their polymerases (those genome-copying enzymes mentioned earlier) are typically less precise than those of DNA viruses, and RNA itself is inherently less stable than DNA. So viruses, and particularly RNA viruses, easily develop resistance to our immune system’s attempts to find and foil them.

The Stanford studies may help reveal whether the precision-targeted “laser” or kitchen-sink “lightbulb” approach works best.

The virus breaks into a cell

Assistant professor of chemical engineering and subcellular-compartment spelunker Monther Abu-Remaileh, PhD, described two key ways the coronavirus breaks into a cell and seeks comfort there, and how it might be possible to bar one of those entry routes with the right kind of drug.

Here’s one way: Once the coronavirus locks on to a cell, its greasy envelope comes into contact with the cell’s equally greasy outer membrane. Grease loves grease. The viral envelope and cell membrane fuse, and the viral contents dump into the cell.

The other way is more complicated. The viral attachment can set off a process in which the area on the cell’s outer membrane nearest the spot where the contact has been made caves in — with the virus (happily) trapped inside — until it gets completely pinched off, forming an inbound, membrane-coated, liquid-centered capsule called an endosome inside the cell. (To visualize this, imagine yourself with a wad of bubble gum in your mouth, blowing an internal bubble by inhaling, and then swallowing it. In this analogy, you’re the cell and all your skin, beginning with your lips, constitutes the cell’s outer membrane.)

Enclosed in this endosome is the viral particle that set the process in motion. The little devil has just hooked itself a ride into the cell’s inner sanctum. At this point, the viral particle consists of its envelope, its capsid and its enclosed genome — a blueprint for the more than two dozen proteins the virus needs and the invaded cell doesn’t provide.

But the endosome doesn’t remain an endosome indefinitely, Abu-Remaileh told me. Its mission is to become another entity called a lysosome, or to fuse with an existing lysosome.

Lysosomes serve as cells’ recycling factories, breaking down large biomolecules into their constituent building blocks for reuse. For this, they need an acidic environment, generated by protein pumps on their surface membranes that force protons into these vesicles.

The building internal acidity activates enzymes that chew up the cloistered coronavirus’s spike proteins. That brings the virus’s envelope in contact with the vesicle membrane and enables their fusion.

The viral genome gets squirted out into the greater expanse of the cell. There, the viral genome will find and commandeer the raw materials and molecular machinery required to carry out its genetic instructions. That machinery will furiously crank out viral proteins — including the customized polymerase SARS-CoV-2 needs to replicate its own genome. Copies of the genome and the virus’s capsid proteins will be brought together and repackaged into viral progeny.

A pair of closely related drugs, chloroquine and hydroxychloroquine, have gotten tons of press but, so far, mostly disappointing results in clinical trials for treating COVID-19. Some researchers advocate using hydroxychloroquine, with the caveat that use should be early in the course of the disease.

In a lab dish, these drugs diffuse into cells, where they diminish acidity in endosomes and prevent it from building up in lysosomes. Without that requisite acidity, the viral-membrane spike proteins can’t be chewed up and the viral envelope can’t make contact with the membrane of an endosome or lysosome. The virus remains locked in a prison of its own device.

That’s what happens in a dish, anyway. But only further clinical trials will tell how much that matters.

How the coronavirus reproduces

SARS-CoV-2 has entered the cell, either by fusion or by riding in like a Lilliputian aquanaut, stealthily stowed inside an endosome. If things go right for the virus, it fuses with the endosome’s membrane and spills its genome out into the (relatively) vast surrounding cellular ocean.

That lonely single strand of RNA that is the virus’s genome has a big job to do — two, in fact, Judith Frydman, PhD, professor of biology and genetics, told me — in order to bootstrap itself into parenting a pack of progeny. It must replicate itself in entirety and in bulk, with each copy constituting the potential seed of a new viral particle. And it must generate multiple partial copies of itself — sawed-off sections that serve as instructions, telling the cell’s protein-making machines, called ribosomes, how to manufacture the virus’s more than two dozen proteins.

To do both things, the virus needs a special kind of polymerase. Every living cell, including each of ours, uses polymerases to copy its DNA-based genome and to transcribe its contents (the genes) into RNA-based instructions that ribosomes can read.

The SARS-CoV-2 genome, unlike ours, is made of RNA, so it’s already ribosome-friendly, but replicating itself means making RNA copies of RNA. Our cells never need to do this, and they lack polymerases that can.

SARS-CoV-2’s genome, though, does carry a gene coding for an RNA-to-RNA polymerase. If that lone RNA strand can find and insert itself into a ribosome, the latter can translate the viral polymerase’s genetic blueprint into a working protein. Fortunately for the virus, there can be as many as 10 million ribosomes in a single cell.

Once made, the viral polymerase cranks out not only multiple copies of the full-length viral genome — replication — but also individual viral genes or groups of them. These snippets can clamber aboard ribosomes and command them to produce the entire repertoire of all the proteins needed to assemble numerous new viral offspring.

These newly created proteins include, notably, more polymerase molecules. Each copy of the SARS-CoV-2 genome can be fed repeatedly through prolific polymerase molecules, generating myriad faithful reproductions of the initial strand.

Well, mostly faithful. We all make mistakes, and the viral polymerase is no exception actually it’s pretty sloppy as polymerases go — much more so than our own cells’ polymerases, Carette and Frydman told me. So the copies of the initial strand — and their copies — are at risk of being riddled with copying errors, aka mutations.

However, coronavirus polymerases, including SARS-CoV-2’s, come uniquely equipped with a sidekick “proofreader protein” that catches most of those errors. It chops out the wrongly inserted chemical component and gives the polymerase another, generally successful, stab at inserting the proper chemical unit into the growing RNA sequence.

Coronavirus birth control

The experimental drug remdesivir, approved for emergency use among hospitalized COVID-19 patients, directly targets RNA viruses’ polymerases.

Stanford participated in clinical trials leading to this injectable drug’s approval. Initially developed for treating Ebola virus infection, it belongs to a class of drugs that work by posing as legitimate chemical building blocks of a DNA or RNA sequence. These poseurs get themselves stitched into the nascent strand and gum things up so badly that the polymerase stalls out or produces a defective product.

“Now, with the drug, the virus starts making a lot of rotten genomes that poison the viral replication process,” said Frydman.

Remdesivir has the virtue of not messing up our cells’ own polymerases, said Robert Shafer, MD, professor of infectious disease, who maintains a continuously updated database of results from trials of drugs targeting SARS-CoV-2.

But while remdesivir’s pretty good at faking out the viral polymerase’s companion proofreader protein, it’s far from perfect, Shafer said. Some intact viral genome copies still manage to be made, escape from the cell, and infect other cells — mission accomplished.

Using remdesivir in combination with some still-sought, as yet undiscovered drug that could block the proofreader might be a more surefire strategy than using remdesivir alone, Shafer said.

The final round in the cellular boxing ring

In addition to replicating its full-length genome, the virus has to make lots of proteins. And it knows just how. Those RNA snippets spun off by the viral polymerase are tailored to play by the cell’s protein-making rules — well, up to a point. They fit into ribosomes exactly as do the cell’s own strands of “messenger RNA” copied from the cell’s genes by its own DNA-reading polymerases. So-called mRNAs are instructions for making proteins.

But there’s a hitch: Among the proteins the virus forces ribosomes to manufacture are some that, once produced, bite the hand that fed them. Certain newly made viral proteins home to ribosomes in the act of reading one or another of the cell’s mRNA strands, hook themselves onto the strand and stick stubbornly, stalling out the ribosome until the cell’s mRNA strand falls apart.

The genomic RNA strands the virus generates, though, all have little blockades on their front ends that protect them from being snagged on the cell’s ribosomes by the viral wrecking crew. The result: The cell’s protein-making assembly line is overwhelmingly diverted to the production of viral proteins. That’s a two-fer: It both increases viral-component production and stifles the infected cell’s natural first line of defense.

Interferons as a potential treatment

Among the cell’s stillborn proteins are molecules called interferons, which the cell ordinarily makes when it senses it’s been infected by a virus. Interferons have ways of monkeying with the viral polymerase’s operations and squelching viral replication. In addition, when secreted from infected cells, interferons act as “call in the troops” distress signals that alert the body’s immune system to the presence and location of the infected cell.

Instead, silence. Advantage: virus.

There are several different kinds of interferons. A clinical trial is underway at Stanford to determine whether a single injection of one of them, called interferon-lambda, can keep just-diagnosed, mildly symptomatic COVID-19 patients out of the hospital, speed recovery and reduce transmission.

If you don’t hate and respect viruses by now, maybe you haven’t been paying attention. But there’s more.

Viruses don’t always kill the cells they take hostage. Some sew their genes into the genome of the cells they’ve invaded, and those insertions add up. Viral DNA sequences make up 8% of our genome — in contrast with the mere 1% that codes for the proteins of which we’re largely made and that do most of the making.

“Our genome has been ‘invaded’ by previous encounters with retroviruses after infection of sperm or egg cells,” Carette told me. “Through evolution, these retroviruses’ genes have become inactive.”

But, as always, there’s an exception. As Carette said: “An ancient viral gene has been repurposed to play an essential role in embryogenesis,” the process by which an embryo forms and develops.

The protein this gene encodes enables the fusion of two kinds of cells in the developing fetus’s placenta, allowing nutrient and waste exchange between the developing embryo and the maternal blood supply.

4. Summary: common themes in ubiquitin dependent cell cycle control

Ubiquitination is an essential regulator of cell cycle progression in all eukaryotes. It controls a wide variety of reactions important for proliferation and development, such as progression through the cell cycle program, function of cell cycle checkpoints, and coordination of proliferation with development. Ubiquitination can exert specific control over so many processes by changing the abundance or the activity of modified proteins. Ubiquitination itself is tightly regulated and carried out by very specific enzymes. Whether a protein is ubiquitinated or not is often determined by a balance of counteracting ubiquitination and deubiquitination activities. Whenever irreversible transitions have to be accomplished, ubiquitination triggers the proteasomal degradation of crucial regulators. Ubiquitin-dependent proteolysis is also used to dispose of activated growth-factor receptors by targeting them to lysosomes. Finally, non-proteolytic ubiquitination exerts cell cycle control by orchestrating events in cell cycle checkpoints. We believe that the multiple layers of regulation provided by ubiquitin hold great promise for future innovative approaches to arrest the proliferation of cancer cells in more efficient and specific ways than currently available.

Left panel: Examples of ubiquitinated proteins, which are not degraded upon their modification. In parentheses, the function of the relevant modification in cell cycle control is noted. Right panel: Examples of proteins that are degraded after being ubiquitinated at different times in the cell cycle. In parenthesis, the relevant ubiquitin ligases are noted.

Watch the video: Cell cycle phases. Cells. MCAT. Khan Academy (January 2023).