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Lecture 17: DNA repair and Recombination - Biology

Lecture 17: DNA repair and Recombination - Biology


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Lecture 17: DNA repair and Recombination

Cohesin regulates homology search during recombinational DNA repair

Homologous recombination (HR) is a ubiquitous DNA double-strand break (DSB) repair mechanism that promotes cell survival. It entails a potentially genome-wide homology search step, carried out along a conserved RecA/Rad51-ssDNA nucleoprotein filament (NPF) assembled on each DSB ends 1–3 . This search is subdued to NPF-dsDNA collision probability, dictated in part by chromatin conformation 2,4 . In contrast to the extensive knowledge about chromatin composition and mobility changes elicited by the DNA damage checkpoint (DDC) 5–7 , whether, how, and to which extent a DSB impacts spatial chromatin organization, and whether this organization in turns influences the homology search process, remains ill-defined 8,9 . Here we characterize two layers of spatial chromatin reorganization following DSB formation in S. cerevisiae. While cohesin folds chromosomes into cohesive arrays of 10-20 kb long chromatin loops as cells arrest in G2/M 10,11 , the DSB-flanking regions locally interact in a resection- and 9-1-1 clamp-dependent manner, independently of cohesin and HR proteins. This local structure blocks cohesin progression, constraining the extending NPF at loop base. Functionally this organization promotes side-specific cis DSB-dsDNA interactions that scales with loop expansion span, and provides a kinetic advantage for identification of intra- over inter-chromosomal homologies. We propose that cohesins regulate homology search by promoting cis dsDNA over-sampling, both upon loop expansion-coupled unidimensional dsDNA scanning, NPF trapping, and chromosome individualization, largely independent of their role in sister chromatid cohesion.


Trends

Of the four known pathways for repairing DNA DSBs, some evolved towards high-fidelity processes (HR and C-NHEJ), while others are intrinsically mutagenic (alt-EJ and SSA).

Some repair pathways are end resection-independent (C-NHEJ), while others are end resection-dependent (HR, alt-EJ, and SSA). End resection likely plays a key role in dictating DNA repair pathway choice.

Homology-based repair pathways (HR, alt-EJ, and SSA) are competitive and mutually regulated around the RAD51 presynaptic and postsynaptic steps of HR.

Error-prone repair pathways can compensate for the loss of HR. Polθ (an alt-EJ polymerase) is upregulated in HR-deficient cancers: loss of the HR and Polθ-mediated alt-EJ pathways is synthetic lethal.

DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.


Introduction

Cellular DNA is constantly altered by endogenous and exogenous factors, resulting in tens of thousands of lesions in a human cell every day (Lindahl, 1993). This damage may be classified into two types according to size: non-bulky DNA and bulky DNA. Non-bulky DNA lesions include base mismatches, abasic sites, and small base modifications, which in general are repaired by mismatch repair (MMR), base excision repair (BER), nucleotide incision repair (NIR), direct reversal repair (DRR), and translesion DNA synthesis (TLS) (Gros et al., 2004 Fortini and Dogliotti, 2007 Sharma et al., 2013 Yi and He, 2013 Ignatov et al., 2017). Bulky DNA lesions include, among other types of damage: double-strand breaks, DNA-protein cross-links (DPCs), and intra- and inter-strand DNA cross-links. The structural complexity of certain bulky DNA lesions requires the use of several DNA repair pathways acting in a coordinated manner, including homologous recombination (HR), non-homologous DNA end-joining (NHEJ), nucleotide excision repair (NER), TLS and BER Fanconi anemia (FA) signaling system and complex proteolytic machinery (Ishchenko et al., 2006 Ho and Schärer, 2010 Duxin et al., 2014 Tretyakova et al., 2015 Martin et al., 2017). Non-bulky DNA lesions cause limited and local DNA perturbations, whereas bulky ones induce significant distortions in the overall DNA helix structure (Ide et al., 2011). DNA-protein cross-links (DPCs) are formed when a protein covalently binds to DNA (Tretyakova et al., 2015). They are difficult to repair because of their super-bulky character compared with known voluminous, helix-distorting DNA lesions, such as UV-induced pyrimidine dimers. These super-bulky adducts can be generated by exposure of cells to endogenous and exogenous cross-linking agents (Stingele et al., 2017 Zhang et al., 2020). The presence of protein covalently attached to DNA strongly interferes with DNA replication, transcription, repair, and chromatin remodeling (Kuo et al., 2007 Klages-Mundt and Li, 2017 Yudkina et al., 2018 Ji et al., 2019). DPCs may be classified into five types, according to the nature of the covalent link in the DNA-protein complex and the presence of DNA strand breaks (Ide et al., 2015, 2018 Nakano et al., 2017). Type 1, the most common type of DPC, is formed when proteins covalently link to a nitrogenous base in undisrupted DNA. Type 2-4 cross-links occur when DNA-cleaving enzymes are trapped in a covalent intermediate with a DNA strand (Ide et al., 2015, 2018 Nakano et al., 2017). Type 2 is formed when bi-functional DNA glycosylases and repair enzymes containing β-lyase activity such as DNA polymerase β and Parp1 irreversibly bind to a cleaved apurinic/apyrimidinic (AP) site (Ide et al., 2015, 2018 Nakano et al., 2017). Type 3 is generated during abortive DNA strand cleavage by topoisomerase 1 (Top1) and formation of a covalent tyrosinyl–phosphodiester bond between the protein and the 3′-terminal DNA phosphate moiety of SSB (Ide et al., 2015, 2018 Nakano et al., 2017). The abortive action of topoisomerase 2 (Top2) generates type 4 DPC, in which tyrosine is linked to the 5′-terminal phosphates of double-strand breaks (DSB) (Ide et al., 2015, 2018 Nakano et al., 2017). Recently, a new type of DPC emerged after the discovery of HMCES, a 5-hydroxymethylcytosine (5hmC) binding protein which can recognize abasic sites in single stranded DNA (ssDNA) and form a covalent ssDNA-HMCES crosslink to prevent error-prone translesion synthesis past the lesion (Mohni et al., 2019). Because of the differences in structure and composition between these five groups, each type of DPC is processed by a distinct repair mechanism. It seems difficult to remove super-bulky Type 1 DPC in the canonical linear DNA excision repair pathways because the presence of a protein molecule blocks access to DNA. Nevertheless, recent studies have revealed that nucleotide excision repair (NER) and homologous recombination (HR) can remove certain types of DPCs in a nuclease-dependent manner (Zhang et al., 2020). However, it is still not clear whether these repair pathways could deal with other types of DPC. Stingele et al. (2017) have proposed that each constituent of DPC: DNA, protein, and the covalent linkage between them might be processed by three different repair mechanisms. A recent paper by Kühbacher and Duxin (2020) provides comprehensive review on the formation and repair of DPCs. In this review, we summarize the current knowledge regarding the repair mechanisms involved in removal of DHCs induced by various genotoxic agents. Covalent cross-linking to DNA occurs more often with DNA binding proteins, such as histones, transcription factors, and DNA metabolizing enzymes including repair factors and topoisomerases (Klages-Mundt and Li, 2017). In the cell nucleus, histones are assembled into an octamer forming the nucleosome core with 147 bp of DNA wrapped around and tightly bound to it (Luger et al., 1997, 2012). This basic chromatin structure makes histones primary targets of DNA cross-linking agents, leading to the formation of DNA-histone cross-links (DHC) (Solomon and Varshavsky, 1985). Currently, the repair mechanisms counteracting DHCs generated by various factors only started to unravel.

DNA-Histone Cross-Links (DHCs)

Nucleosomal DNA is packaged into compact units referred as chromosomes, in which core nucleosome particles are connected by stretches of linker DNA up to 80 bp length. A nucleosome core particle (NCP) is composed of two copies each of histones H2A, H2B, H3, and H4. The molecular weight of individual histones range from 11 to 22 KDa, whereas the molecular weight of histone octamer in NCP is 210 KDa (Eickbush and Moudrianakis, 1978 Luger et al., 1997). The stability of the nucleosome is based on various protein-protein interactions, and numerous non-covalent electrostatic and hydrogen bonds between histones and the DNA duplex (Luger et al., 1997, 2012 Davey et al., 2002 Rohs et al., 2009). The primary structure of chromatin can be depicted as a beads-on-a-string organization of individual nucleosomes, which can be further folded into compact secondary and tertiary structures, with the help of histone variants present in certain nucleosomes and post-translational modifications (PTMs) situated in disordered histone tails (Woodcock and Dimitrov, 2001 Luger et al., 2012). The folding of chromatin into primary, secondary, and tertiary structures is crucial for regulating the accessibility of DNA to complex multi-protein machinery involved in DNA replication, transcription, and repair. Non-covalent interactions between DNA and histones enable chromatin dynamics to switch between the closed and open conformations. DHCs impair chromatin flexibility, which may subsequently affect long-distance interactions in chromatin that would indirectly disturb DNA replication, transcription, and repair within a topologically associating domain (TAD) (Hinz et al., 2010 Todd and Lippard, 2010 Tretyakova et al., 2015 Hauer and Gasser, 2017 Nakano et al., 2017). DHCs belong to type 1, a non-enzymatic form of DPC, in which a protein is covalently attached to an undisrupted DNA (Ide et al., 2011). Several comprehensive studies describing the mechanisms of formation of DHCs have been published recently (Ming et al., 2017 Shang et al., 2019 Yang and Greenberg, 2019), nevertheless, it is not known whether specific repair mechanisms for the removal of DHCs exist. In this review, we focus mainly on the repair pathways of DHCs and briefly describe their formation.

Formation of DHCs

A water-soluble covalent complex of DNA and histones (H2A and H2B) was first identified in a UV cross-linking assay (Smith, 1966 Sperling and Sperling, 1978). With this finding, it became evident that UV irradiation can induce DHCs in addition to well-known pyrimidine dimers. It was then discovered that exogenous and endogenous aldehydes could also form DHCs in cells (Lam et al., 1985 Kuykendall and Bogdanffy, 1992). More than 10% of amino acid residues in histones are lysines, whereas, aldehydes preferentially react with ε-amino groups of lysine side-chains with the formation of a Schiff base, which further reacts with exocyclic amino groups of guanine, adenine, and cytosine DNA bases, creating methylene linkage. Many cross-linking agents, such as chromate, metal ions, and cisplatin (cis-diaminedichloroplatinum-II), also induce DHCs in cells (Zhitkovich and Costa, 1992). Platinum compounds not only cause DNA-DNA cross-links but also covalently link DNA-protein complexes. In the case of histones (Figure 1A), these compounds cross-link ε-amino-groups of lysines and N 7 atoms of guanosines (Tretyakova et al., 2015 Ming et al., 2017). Cross-links between DNA and methionine residues were also observed in an X-ray structure of nucleosomes treated with platinum compounds (Wu et al., 2008). Exposure of purified nucleosome to bi-functional alkylating agents (e.g., nitrogen mustards) also cross-links histones to guanosines in DNA (Shang et al., 2019) however, these types of cross-links in cells are much less abundant than DNA cross-links with cysteines and histidines of non-histone proteins (Loeber et al., 2009).

Figure 1. Mechanisms of histone-DNA cross-links formation. (A) Reaction mechanisms of DNA cross-linking agents. (B) Direct cross-linking of histones to modified DNA bases. (C) Abasic site mediated cross-linking of histones to DNA. NCP-NH2: N-terminal amine (Lysine) of histones in the nucleosome core.

Histones can also directly react with 5-formylcytosine, a naturally occurring modified DNA base, and 8-oxoguanine, a major oxidative DNA damage product. Lysine amino groups react with 5-formylcytosine (Figure 1B), with the formation of a reversible Schiff base (Li et al., 2017 Raiber et al., 2018). The reaction of lysine side-chains with 8-oxoguanosine produced a stable protein cross-linked spiroiminodihydantoin (Sp) adduct (Xu et al., 2008).

Finally, the majority of DHCs are produced by a reaction between histone lysines and an aldehyde form of the 2′-deoxyribose at apurinic/apyrimidinic (AP) sites (Figure 1C) that are either directly formed upon damage or generated during excision of damaged bases in the base excision repair pathway (Solomon and Varshavsky, 1985 Sczepanski et al., 2010). The resulting Schiff base often undergoes strand-breaking ß-elimination, followed by a reversal of a histone-DNA cross-link. Since histone emerges unaltered from the reaction, the whole process is sometimes referred to as histone-catalyzed strand cleavage at AP sites (Ren et al., 2019). It should be noted that histone PTMs and the chromatin state could have a significant impact on DHC formation at abasic sites and with DNA bases (Sczepanski et al., 2010 Bowman and Poirier, 2015).

Mechanisms of Repair of DHC

Although DPCs, especially DHCs, often occur in cells and present a constant threat to genome stability, it is presumed that, except for tyrosyl-DNA phosphodiesterases, there is no specialized DNA repair pathway dedicated to meet these super-bulky challenges. Instead, the cell employs several distinct DNA repair and protein degradation mechanisms to target cross-linked DNA and protein/histone components in a given DPC/DHC. The covalently bound protein could be detected and degraded to a small peptide by cell proteolytic machinery, such as the specialized proteases SPRTN/Wss1, Ddi1, and GCNA1, or by proteasome, an ATP-dependent multi-subunit protease complex, whereas the damaged DNA component is detected and repaired in the NER, BER, HR, NHEJ, and FA pathways.

Proteasome-Dependent Proteolysis of Histones Cross-Linked to DNA

Proteasome-mediated proteolysis is the major pathway for the degradation of damaged proteins in a cell. A 26S proteasome consists of a cylindrical 20S core particle and one or two 19S regulatory particles (Ciechanover, 1998 Lecker et al., 2006). Although 20S core can bind to different regulatory particles, only the 19S particle confers the ability to degrade ubiquitylated proteins (Coux et al., 1996 Adams, 2004 Stadtmueller and Hill, 2011). Considering the vital role of the proteasome in the degradation of damaged protein, proteasome and ubiquitin involvement in the proteolysis of DHCs or DPCs remains a topic of debate. Inhibition of proteasome in Xenopus egg extracts did not stabilize the DPCs (Nakano et al., 2007 Duxin et al., 2014). However, many studies of the repair of DPCs in mammalian cells suggest proteasome participation (Adams, 2004 Baker et al., 2007 Zecevic et al., 2010 Larsen et al., 2019). Proteasome involvement in DHC removal surfaced for the first time in the research of Quievryn and Zhitkovich (2000), who discovered that proteasome inhibitors prevent the removal of DHCs and sensitize human cells to lower levels of formaldehyde. A study in Xenopus egg extracts found that DPCs are ubiquitylated by TRAIP E3 ubiquitin ligase and are subsequently degraded by the proteasome (Duxin et al., 2014 Larsen et al., 2019). However, an earlier study clearly demonstrated that DPCs are not marked with polyubiquitin chains, but are nevertheless subjected to proteasomal degradation by a mechanism that is not well understood (Nakano et al., 2009). The 26S proteasome can degrade purified non-ubiquitylated histones (Kisselev et al., 2006), raising the possibility of proteasomal degradation of non-ubiquitylated damaged histones in cells. A couple of studies have demonstrated that during replication stress induced by genotoxic agents, histones are hyperacetylated, and then specifically degraded in a ubiquitin-independent manner by a complex of 20S proteasome with PA200 proteasome activator, a distinct regulatory particle (Qian et al., 2013 Mandemaker et al., 2018). Although these studies have demonstrated that the ubiquitin-independent degradation of acetylated histones alleviates replication stress, the additional function of PA200-20S proteasome in DHC repair cannot be excluded. Moreover, PA200 was detected in nuclear speckles, and its role in DNA repair has been proposed (Ustrell et al., 2002). Thus, more detailed understanding of the role of proteasome in DHC repair requires further investigation.

The 20S proteasome is a hollow, barrel-shaped particle composed of 28 non-identical subunits arranged into four stacked rings. The active sites are sequestered inside an internal cavity separated from regulatory 19S and PA200 complexes by a gated channel. This 13Å channel is too narrow for a folded protein to enter (Löwe et al., 1995 Groll et al., 1997). For complete degradation of a DNA-cross-linked protein, the cross-linked DNA nucleotide itself would have to enter the proteolytic chamber, pulling a DNA strand inside. However, the DNA component of a DPC might be too bulky to enter the channel. Therefore, proteasome can remove only part of a cross-linked protein, converting DHC into a smaller DNA-peptide cross-link. Alternatively, traditional proteases, in which an active site is located in a cleft on the enzyme surface, could be involved in excision of the bulk of the non-cross-linked polypeptide chain, which can then be degraded by any of these proteases and by the proteasome.


Real-time analysis of double-strand DNA break repair by homologous recombination

The ability to induce synchronously a single site-specific double-strand break (DSB) in a budding yeast chromosome has made it possible to monitor the kinetics and genetic requirements of many molecular steps during DSB repair. Special attention has been paid to the switching of mating-type genes in Saccharomyces cerevisiae, a process initiated by the HO endonuclease by cleaving the MAT locus. A DSB in MATa is repaired by homologous recombination--specifically, by gene conversion--using a heterochromatic donor, HMLα. Repair results in the replacement of the a-specific sequences (Ya) by Yα and switching from MATa to MATα. We report that MAT switching requires the DNA replication factor Dpb11, although it does not require the Cdc7-Dbf4 kinase or the Mcm and Cdc45 helicase components. Using Southern blot, PCR, and ChIP analysis of samples collected every 10 min, we extend previous studies of this process to identify the times for the loading of Rad51 recombinase protein onto the DSB ends at MAT, the subsequent strand invasion by the Rad51 nucleoprotein filament into the donor sequences, the initiation of new DNA synthesis, and the removal of the nonhomologous Y sequences. In addition we report evidence for the transient displacement of well-positioned nucleosomes in the HML donor locus during strand invasion.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Schematic of S. cerevisiae mating…

Schematic of S. cerevisiae mating type loci on chromosome III and the SDSA…

High-resolution kinetics of MAT a…

High-resolution kinetics of MAT a switching to MAT α. ( A ) Representative…

Dpb11 is required for MAT…

Dpb11 is required for MAT switching. Southern blots show progression of MAT a…

Both sides of a DSB at MAT interact with homologous HML donor sequences.…

Comparison of NH-tail clipping in…

Comparison of NH-tail clipping in MAT switching WT and rad54 Δ/ rdh54 Δ…

Heterochromatic nucleosomes within HML are…

Heterochromatic nucleosomes within HML are remodeled during MAT switching. ( A ) Nucleosome…


Transcription-coupled Repair

Base excision repair (BER) and nucleotide excision repair (NER) are different pathways involved in the removal of many common DNA lesions. Oxidatively damaged bases are primarily corrected via the BER pathway, whereas helix-distorting lesions caused by exposure to chemical mutagens or ultraviolet light are removed via NER. Both pathways can remove damage throughout the genome, but in both humans and yeast damage on the template strand of actively transcribed genes is removed much more rapidly than other damage. Efforts to verify that this transcription-coupled repair (TCR) occurs in Drosophila, however, failed to find evidence for its existence, at least for the two main classes of UV-induced damage (de Cock et al. 1992 van der Helm et al. 1997).

Cockayne syndrome is a hereditary disorder that results from disruption of TCR (for review see van Gool et al. 1997). This disease can result from mutations of any of several genes, including the NER genes XPB, XPD, and XPG, as well as the non-NER genes CS-A and CS-B. CS-B encodes a polypeptide with an ATPase domain similar to that of Swi/Snf-type chromatin remodeling proteins. CS-A encodes a WD-repeat protein that interacts with CSA and with the RNA polymerase II basal transcription factor TFIIH. The S. cerevisiae protein Rad26 is highly similar to CSB, showing ∼50% amino acid identity over 500 residues Rad28 is the yeast homologue of CSA. The Drosophila genome does not encode apparent homologues of either CSA or CSB. Thus, both the absence of sequence conservation and, more directly, experimental results indicate that TCR does not occur in Drosophila.

What are the consequences of lack of TCR? The importance of this pathway in humans is evidenced by the severity of Cockayne syndrome, whose features include neurological abnormalities, prenatal growth defects, and severe postnatal developmental failure, resulting in early death. A model for the mechanism of TCR has emerged recently (Le Page et al. 2000). The types of damage repaired by BER and NER often block RNA polymerase, resulting in a stalled polymerase complex that remains stably associated with the damaged template strand. A critical function of the TCR machinery is to remove this stalled complex to allow repair proteins to access and correct the damage. At least some of the repair machinery is recruited to the site by the TCR complex.

Drosophila cells apparently lack at least the process that allows rapid removal of DNA damage from template strands of transcribed genes. How do these cells deal with stalled RNA polymerase complexes? One possibility is that they don't. Most cell growth and division in Drosophila occurs during larval development. Larval tissues are typically polyploid or polytene during this time, so the absence of one template for transcription may not be detrimental in many cases. Cells that contribute to the adult are diploid, but the animal can suffer the loss or slow growth of a substantial fraction of these cells without apparent consequences. Nonetheless, if stalled transcription complexes were not removed, one would expect to observe the reverse of TCR: slower repair of template strands. For the genes analyzed, both strands were repaired with similar time courses for both transcribed and nontranscribed genes (de Cock et al. 1992 van der Helm et al. 1997). It is likely that some other mechanism is used to remove stalled RNA polymerase complexes in Drosophila. One possibility is that these stalled complexes have a much shorter half-life in Drosophila than in mammalian cells. Alternatively, there may be an active mechanism to remove stalled complexes without recruitment of repair proteins.

It is formally possible that TCR of oxidative damage does exist in Drosophila, since only repair of UV-induced damage has been measured. However, the failure to identify homologues of CSA and CSB in the genome sequence suggests that this is not the case.


Is Competence a Stress Response that Substitutes for SOS?

Almost all bacterial phyla harbor a lexA gene with characteristic SOS boxes [1]. Whilst the SOS response plays an important role in the lifestyle and virulence of a number of significant pathogens, nevertheless, not all pathogens possess an SOS response. Notable pathogens that lack an SOS response are: Campylobacter jejuni, Streptococcus pneumoniea, Streptococcus pyogenes, Legionella pneumophila, Helicobacter pylori, Neisseriae meningititis, and Neisseriae gonorherae. In S. pneumoniae, L. pneumophila, and H. pylori, antibiotics provoke the induction of competence for transformation therefore, in these species competence might substitute for SOS [18]. Competence has been hypothesized to enable DNA uptake as a nutrient to serve as a template for DNA damage repair or for genetic exchange. Nevertheless, in these three species competence is not induced by the same antibiotics, which indicates a specific fine-tuning of the response. The correlation between a lack of SOS response and competence induction by antibiotics warrants examination among other naturally competent pathogens.


<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More. </a></p> Function i

Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks (PubMed:9774452, PubMed:24798879, PubMed:32457312, PubMed:11459989, PubMed:12205100, PubMed:27264870).

Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Plays also an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA (By similarity).

<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More. </a></p> Manual assertion inferred from sequence similarity to i

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More. </a></p> Manual assertion based on experiment in i


Homologous Recombination, but Not DNA Repair, Is Reduced in Vertebrate Cells Deficient in RAD52

Fig. 1 . Strategy of disruption of the RAD52 gene. (A) Schematic representation of part of the RAD52 locus, the two gene disruption constructs, and the configuration of the targeted loci. Solid boxes indicate the positions of exons numbers show the 3′ nucleotide of each exon relative to the start codon (4). Relevant EcoRI recognition sites are indicated by RI. (B) Southern blot analysis of EcoRI-digested DNA from the indicated genotypes with the probe shown in panel A. The positions and sizes of the hybridizing fragments of the wild-type and targeted loci are indicated. (C) Northern blot analysis of total RNA with the full-length chicken RAD52 cDNA as a probe. The same filter was rehybridized with a chicken β-Actin probe (7).

Effects of Rad52 deficiency on sensitivity to DNA-damaging agents, Rad51 focus formation, and Ig gene conversion.

Fig. 2 . Sensitivity of the indicated clones to DNA-damaging agents. The fractions of colonies surviving after the indicated treatment of cells compared to nontreated controls of the same genotype are shown on the y axis on a logarithmic scale. (A) Ionizing radiation (B) MMS (C) cisplatin. The radiation doses and the MMS and cisplatin concentrations are displayed on the x axis on a linear scale in each graph. Data shown are the means ± standard deviations of at least three separate experiments. Fig. 3 . Immunofluorescent visualization of Rad51. At the time indicated after 8-Gy γ-irradiation, wild-type andRAD52 −/− cells were analyzed. Controls were stained with normal rabbit serum followed by FITC-conjugated anti-rabbit IgG and are overexposed relative to the experimental frames.

Reduced targeted integration frequencies inRAD52 −/− cells.

Fig. 4 . Measurement of targeted integration frequencies at theIgλ locus. (A) Schematic representation of part of the rearranged Igλ locus and the disruption construct (Igλ-neo). ΨV1, first pseudogene L, leader sequence Vλ, variable gene segment Jλ, joining gene segment Cλ, constant gene segment. BglI (BgI), BglII (BgII), andXbaI (X) restriction sites are indicated. Not allBglI sites in this region are shown. (B) Histograms of sIgM expression of wild-type (a and b), RAD52 −/− (c and d), and RAD52 cDNA-reconstitutedRAD52 −/− (RAD52R) (e and f) clones after no transfection (a) or transfection of Igλ-neo and G418 selection of transfectants of each clone (b to f). Thex and y axes show the fluorescence intensity from an FITC-conjugated anti-IgM polyclonal antibody on a logarithmic scale and the cell number on a linear scale in each graph, respectively. The percentage of cells losing sIgM expression is shown in each panel.

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workCorrespondence to: Alda Corrado, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy, Tel.: +390502211524, Fax: +390502211527, E-mail: [email protected] or Barbara Pardini, Italian Institute for Genomic Medicine (IIGM), Via Nizza 52, 10126 Turin, Italy, Tel.: +390116709542, Fax: +390112365601, E-mail: [email protected] Search for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workCorrespondence to: Alda Corrado, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy, Tel.: +390502211524, Fax: +390502211527, E-mail: [email protected] or Barbara Pardini, Italian Institute for Genomic Medicine (IIGM), Via Nizza 52, 10126 Turin, Italy, Tel.: +390116709542, Fax: +390112365601, E-mail: [email protected] Search for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

Italian Institute for Genomic Medicine (IIGM), Turin, Italy

Department of Medical Sciences, University of Turin, Turin, Italy

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD

Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU), Nantes, France

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

School of Public Health, University of Washington, Seattle, WA

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

Kaiser Permanente Medical Care Program of Northern California, Oakland, CA

Epidemiology Research Program, American Cancer Society, Atlanta, GA

Public Health Sciences, University of Virginia, Charlottesville, VA

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA

Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

Stanford University School of Medicine, Stanford, CA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

Melbourne School of Population Health, The University of Melbourne, Melbourne, VIC, Australia

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Melbourne School of Population Health, The University of Melbourne, Melbourne, VIC, Australia

Epidemiology Program, Research Cancer Center of Hawaii, University of Hawaii, Honolulu, HI

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Health Sciences Research, Mayo Clinic Arizona, Scottsdale, AZ

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

Broad Institute of MIT and Harvard, Cambridge, MA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Department of Biology, University of Pisa, Pisa, Italy

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Italian Institute for Genomic Medicine (IIGM), Turin, Italy

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Italian Institute for Genomic Medicine (IIGM), Turin, Italy

Department of Medical Sciences, University of Turin, Turin, Italy

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workCorrespondence to: Alda Corrado, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy, Tel.: +390502211524, Fax: +390502211527, E-mail: [email protected] or Barbara Pardini, Italian Institute for Genomic Medicine (IIGM), Via Nizza 52, 10126 Turin, Italy, Tel.: +390116709542, Fax: +390112365601, E-mail: [email protected] Search for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workCorrespondence to: Alda Corrado, Department of Biology, University of Pisa, Via Derna 1, 56126 Pisa, Italy, Tel.: +390502211524, Fax: +390502211527, E-mail: [email protected] or Barbara Pardini, Italian Institute for Genomic Medicine (IIGM), Via Nizza 52, 10126 Turin, Italy, Tel.: +390116709542, Fax: +390112365601, E-mail: [email protected] Search for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

Italian Institute for Genomic Medicine (IIGM), Turin, Italy

Department of Medical Sciences, University of Turin, Turin, Italy

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD

Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU), Nantes, France

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

School of Public Health, University of Washington, Seattle, WA

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

Kaiser Permanente Medical Care Program of Northern California, Oakland, CA

Epidemiology Research Program, American Cancer Society, Atlanta, GA

Public Health Sciences, University of Virginia, Charlottesville, VA

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA

Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

Stanford University School of Medicine, Stanford, CA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

Melbourne School of Population Health, The University of Melbourne, Melbourne, VIC, Australia

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Melbourne School of Population Health, The University of Melbourne, Melbourne, VIC, Australia

Epidemiology Program, Research Cancer Center of Hawaii, University of Hawaii, Honolulu, HI

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Health Sciences Research, Mayo Clinic Arizona, Scottsdale, AZ

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

Broad Institute of MIT and Harvard, Cambridge, MA

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

Department of Biology, University of Pisa, Pisa, Italy

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Italian Institute for Genomic Medicine (IIGM), Turin, Italy

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Department of Biology, University of Pisa, Pisa, Italy

B.P., A.C., U.P., A.N., and S.L. contributed equally to this workSearch for more papers by this author

Abstract

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10 −6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10 −6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10 −6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.


James E Haber

Repair of broken chromosomes. Genetics and molecular biology of yeast meiotic and mitotic recombination. Control of recombination donor accessibility (donor preference in mating-type switching). Analysis of mutations arising during DNA repair. Chromosome dynamics. Regulation of the DNA damage response and checkpoints induction of damage-induced autophagy.

Member of the US National Academy of Sciences, Fellow of the American Academy of Microbiology, Fellow, American Association of Arts and Sciences. Fellow, American Association for the Advancement of Science. Thomas Hunt Morgan Medal for Lifetime Achievement in Genetics from the Genetics Society of America. Webpage

BIOL 91g Introduction to Research Practice
BIOL 122a Molecular Genetics
BIOL 163b Repairing and Editing the Genome
BIOL 200a Proseminar
BIOL 316a Mechanisms of Recombination
BIOL 316b Mechanisms of Recombination

2011 Genetics Society of America Thomas Hunt Morgan Medal for lifetime achievement in genetics (2010)

Member, National Academy of Sciences (2010)

Member, American Academy of Arts and Sciences (2009)

Radcliffe Institute Fellowship for 2008/9 (2008)

elected Secretary Genetics Society of America (2006)

Elected Fellow, American Association for the Advancement of Science (2005)

Keynote Speaker, Keystone Symposium on Mechanisms of DNA Replication and Recombination (2005)

Director, Genetics Society of America (2003)

Keynote Speaker FASEB Summer Research Conference on Recombination (2003)

John Simon Guggenheim Fellowship (2001)

Giovanni Magni Lecturer, Milan, Italy (2000 - 2001)

Guggenheim Foundation Fellowship (1999)

Abraham and Etta Goodman Chair in Biology (1996)

Fellow, American Academy of Microbiology (1996)

Sloan Foundation Sabbatical Supplement (1990)

National Science Foundation Postdoctoral Fellowship (1970)

US Public Health Service Traineeship (1965 - 1969)

Woodrow Wilson Fellowship (honorary) (1965)

Ait Saada, A, Costa, A, Guo, W, Sheng, Z, Haber, JE Lobachev, K. "Structural parameters of palindromic repeats determine the specificity of nuclease attack of secondary structures." Nuc. Acids Res. (in press). (2021). (forthcoming)

Arnould C, Rocher V, Finoux AL, Clouaire T, Li K, Zhou F, Caron P, Mangeot PE, Ricci EP, Mourad R, Haber JE, Noordermeer D, Legube G. "Loop extrusion as a mechanism for formation of DNA damage repair foci.." Nature 590 (2021): 660-665.

Gallagher DN, Pham N, Tsai AM, Janto AN, Choi J, Ira G, Haber JE. "A Rad51-independent pathway promotes single-strand template repair in gene editing.." PLoS Genetics 16. (2021): e1008689. doi: 10.1371.

Garcia Fernandez F, Lemos B, Khalil Y, Batrin R, Haber JE, Fabre E.. "Chromosome structure due to phospho-mimetic H2A modulates DDR through increased chromatin mobility.." J Cell Sci. doi: 10.1242/jcs.258500. Online ahead of print.. (2021).

Klionsky, DJ et al.. "Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).." Autophagy (2021): doi: 10.1080/15548627.2020.1797280.

Li K, Bronk G, Kondev J, Haber JE. "Yeast ATM and ATR kinases use different mechanisms to spread histone H2A phosphorylation around a DNA double-strand break.." Proc Natl Acad Sci USA 117. (2021): 21354-21363.

Pham, N, Yan, Z, Yu, Y, Afreen, MA, Malkova, A, Haber, JE, Ira, G. "Mechanisms restraining Break-Induced Replication at two-ended DNA double-strand breaks." EMBO J (2021): (in press).

Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F, Demeulemeester J, Santamarina M, Ju YS, Temes J, Garcia-Souto D, Detering H, Li Y, Rodriguez-Castro J, Dueso-Barroso A, Bruzos AL, Dentro SC, Blanco MG, Contino G, Ardeljan D, Tojo M, Robe. "Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition." Nature Genet 52. (2021): 306-319.

Yamaguchi, M and Haber, James E. "Monitoring Gene Conversion in Budding Yeast by Southern Blot Analysis.." Methods Mol Biol . vol. 2153, 2021. 221-238.

Akdemir KC, Le VT, Chandran S, Li Y, Verhaak RG, Beroukhim R, Campbell PJ, Chin L, Dixon JR, Futreal PA PCAWG Structural Variation Working Group PCAWG Consortium.. "Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.." Nature Genet 52. (2020): 294-305.

Bailey MH, Meyerson WU, Dursi LJ, Wang LB, Dong G, Liang WW, Weerasinghe A, Li S, Li Y, Kelso S MC3 Working Group PCAWG novel somatic mutation calling methods working group, Saksena G, Ellrott K, Wendl MC, Wheeler DA, Getz G, Simpson JT, Gerstein MB, D. "Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.." Nature Communications 11. (2020): doi: 10.1038/s41467-020-18151-y..

Braberg H, Echeverria I, Bohn S, Cimermancic P, Shiver A, Alexander R, Xu J, Shales M, Dronamraju R, Jiang S, Dwivedi G, Bogdanoff D, Chaung KK, Hüttenhain R, Wang S, Mavor D, Pellarin R, Schneidman D, Bader JS, Fraser JS, Morris J, Haber JE, Strahl BD,. "Genetic interaction mapping informs integrative structure determination of protein complexes.." Science 370. eaaz4910. doi: 10.1126/science.aaz4910 (2020).

Cortés-Ciriano I, Lee JJ, Xi R, Jain D, Jung YL, Yang L, Gordenin D, Klimczak LJ, Zhang CZ, Pellman DS PCAWG Structural Variation Working Group, Park PJ PCAWG Consortium.. "Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing.." Nature Genet 52. (2020): 331-341.

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. "Pan-cancer analysis of whole genomes.." Nature 578. (2020): 82-93.

Li CH, Prokopec SD, Sun RX, Yousif F, Schmitz N PCAWG Tumour Subtypes and Clinical Translation, Boutros PC PCAWG Consortium.. "Sex differences in oncogenic mutational processes.." Nature Communications 11. (2020): doi: 10.1038/s41467-020-17359-2.

Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K, Khurana E, Waszak S, Korbel JO, Haber JE, Imielinski M PCAWG Structural Variation Working Group, Weischenfeldt J, Beroukhim R, Campbell PJ PCAWG Consortium.. "Patterns of somatic structural variation in human cancer genomes." Nature 578. 7793 (2020): 112-121.

Rheinbay E, Nielsen MM, Abascal F, Wala JA, Shapira O, Tiao G, Hornshøj H, Hess JM, Juul RI, Lin Z, Feuerbach L, Sabarinathan R, Madsen T, et al.. "Analyses of non-coding somatic drivers in 2,658 cancer whole genomes." Nature 578. 7793 (2020): 102-111.

Sieverling L, Hong C, Koser SD, Ginsbach P, Kleinheinz K, Hutter B, Braun DM, Cortés-Ciriano I, Xi R, Kabbe R, Park PJ, Eils R, Schlesner M PCAWG-Structural Variation Working Group, Brors B, Rippe K, Jones DTW, Feuerbach L PCAWG Consortium.. "Genomic footprints of activated telomere maintenance mechanisms in cancer." Nature Communications 11. (2020): 733. doi: 10.1038/s41467-019-13824-9.

Waterman DP, Haber JE, Smolka MB. "Checkpoint Responses to DNA Double-Strand Breaks.." vol. 89 Ed. Annu Rev Biochem. 2020. 103-133..

Zhang Y, Chen F, Fonseca NA, He Y, Fujita M, Nakagawa H, Zhang Z, Brazma A PCAWG Transcriptome Working Group PCAWG Structural Variation Working Group, Creighton CJ PCAWG Consortium.. "High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.." Nature Communications 11. (2020): 76 doi: 10.1038/s41467-019-13885-w.

Broken Chromosome Repair by Homologous Recombination . performer/writer Haber, James E. iBiology: https://www.ibiology.org/genetics-and-gene-regulation/homologous-recombination/#part-1, 2019.

Molecular Mechansims of Repairing a Broken Chromosome . performer/writer Haber, James E. iBiology: https://www.ibiology.org/genetics-and-gene-regulation/homologous-recombination/#part-2, 2019.

Mutations Arising During REpair of a Broken Chromosome . Haber, James E. iBiology: https://www.ibiology.org/genetics-and-gene-regulation/homologous-recombination/#part-3, 2019.

Haber, James E. "DNA Repair: The Search for Homology." Bioessays 40. (2019): e1700229.

Klein, H.L., Bacinskaja, G., Che, J., Cheblal, A., Elango, R., Epshtein, A., Fitzgerald, D.M., Gomez-Gonzalez, B., Khan, S.R., Kumar, S., et al.. "Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways.." Microb Cell 6. (2019): 1-64..

Memisoglu, G and Haber, J E. "Dephosphorylation of the Atg1 kinase complex by type 2C protein phosphatases." Molecular & Cellular Oncology 6. 3 (2019): e1588658.

Memisoglu, G., Eapen, V.V., Yang, Y., Klionsky, D.J., and Haber, J.E.. "PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex.." Proc Natl Acad Sci U S A 116. (2019): 1613-1620..

Thon, G., Maki, T., Haber, J.E., and Iwasaki, H.. "Mating-type switching by homology-directed recombinational repair: a matter of choice.." Curr Genet 65. (2019): 351-362.

Waterman, D.P., Zhou, F., Li, K., Lee, C.S., Tsabar, M., Eapen, V.V., Mazzella, A., and Haber, J.E.. "Live cell monitoring of double strand breaks in S. cerevisiae." PLoS Genet 15. (2019): e1008001..

Botchkarev, VV, Haber, James E. "Functions and regulation of the polo-like kinase Cdc5 in the absence and presence of DNA damage.." Curr Genet 64. (1) (2018): 87-96.

Dwivedi, G, Haber, James E. "Assaying mutations associated with gene conversion repair of a double-strand break.." Methods Enzymol. 601. (2018): 145-160.

Gallagher, DN, Haber, James E. "Repair of a site-specific DNA cleavage: Old-school lessons for Cas9-mediated gene editing.." ACS Chem Biol 13. (2) (2018): 397-405.

Garbacz, MA, Lujan, SA, Burkholder, AB, Cox, PB, Wu, Q, Zhou, ZX, Haber, JE, Kunkel, TA. "Evidence that DNA polymerase delta contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae.." Nat Commun 9. (1) (2018): 858.

Lemos, BR, Kaplan, AC, Bae JE, Ferrazzoli, AE, Kuo, J, Anand RP, Waterman, DP, Haber, James E. "CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.." Proc Natl Acad Sci USA 115. (9) (2018): E2040-E2047.

Maki, T., Ogura, N., Haber, J.E., Iwasaki, H., and Thon, G.. "New insights into donor directionality of mating-type switching in Schizosaccharomyces pombe. PLoS Genet 14, e1007424.." PLoS Genet 14. (2018): e1007424.

Roy, K.R., Smith, J.D., Vonesch, S.C., Lin, G., Tu, C.S., Lederer, A.R., Chu, A., Suresh, S., Nguyen, M., Horecka, J., Tripathi A, Burnett WT, Morgan MA,, Schulz J, Orsley KM, Wei W, Aiyar RS, Davis RW, Bankaitis VA Haber JE. "Multiplexed precision genome editing with trackable genomic barcodes in yeast.." Nat Biotechnol 36. (2018): 512-520..

Anand, R, Beach, A, Li, K, Haber, James E. "Rad51-mediated double-strand break repair and mismatch correction of divergent substrates.." Nature 544. (7650) (2017): 377-380.

Botchkarev VV, Jr., Garabedian MV, Lemos B, Paulissen E, Haber JE.. "The budding yeast Polo-like kinase localizes to distinct populations at centrosomes during mitosis." Mol Biol Cell (2017): mbc.E16-05-0324 ahead of print.

Eapen, VV, Waterman, DP, Bernard, A, Schiffman, N, Sayas, E, Kamber, R, Lemos, B, Memisoglu, G, Ang, J, Mazella, A, Haber, James E. "A pathway of targeted autophagy is induced by DNA damage in budding yeast.." Proc Natl Acad Sci USA 114. (7) (2017): E1158-E1167.

Mehta A, Beach A, Haber JE.. "Homology Requirements and Competition between Gene Conversion and Break-Induced Replication during Double-Strand Break Repair." Mol Cell 65. (2017): 515-26.

Wang, RW, Lee, CS, Haber, James E. "Position effects influencing intrachromosomal repair of a double-strand break in budding yeast.." PLoS One 12. (7) (2017): e0180994.

Haber, James E. "A Life Investigating Pathways That Repair Broken Chromosomes." Annu Rev Genet 50. (2016): 1-28.

Haber, James E. "Asf1 facilitates dephosphorylation of Rad53 after DNA double-strand break repair." Genes Dev 30. (10) (2016): 1211-1224.

Haber, James E. "The rule of three." Nat Rev Mol Cell Biol 17. (2016): 10.1038.

Jain, S., Sugawara, N. and Haber, James E. "Role of Double-Strand Break End-Tethering during Gene Conversion in Saccharomyces cerevisiae." PLoS Genetics (in press). (2016).

Jasin M, Haber JE.. "The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.." DNA Repair (Amst) 44. (2016): 6-16.

Klionsky, D.J., Abdelmohsen, K., Abe, A., Abedin, M.J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C.M., Adams, P.D., Adeli, K., et al.. Guidelines for the use and interpretation of assays for monitoring autophagy . 3rd ed. 2016.

Lee, C.S., Wang, R.W, Chang, H.H., Capurso, D., Segal, M.R., Haber, J.E.. "Chromosome position determines the success of double-strand break repair." Proc Natl Acad Sci USA 113. (2016): E146-154.

Nakajima, Y., Haber, J.E.. "Chromosomes at loose ends." Nat Cell Biol 18. (2016): 257-259.

Tsabar M, Haase J, Harrison B, Snider CE, Eldridge B, Kaminsky L.,Hine, R., Haber, J.E. and Bloom, K.. "A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere." PLoS Genet. 12. (2016): e1006021.

Tsabar M, Hicks WM, Tsaponina O, Haber JE. "Re-establishment of nucleosome occupancy during double-strand break repair in budding yeast.." DNA Repair (Amst) 47. (2016): 21-29.

Vinay V. Eapen, David P. Waterman, Brenda Lemos and James E. Haber. "REGULATION OF THE DNA DAMAGE RESPONSE BY AUTOPHAGY." AUTOPHAGY: Cancer, Other Pathologies, Inflammation, Immunity, Infection and Aging . vol. 10 Ed. M.A. Hayat. Elsevier, 2016. (in press).

Yimit, A., Kim, T., Anand, R., Meister, S., Ou, J., Haber, J.E., Zhang, Z. and Brown, G.W.. "MTE1 Functions with MPH1 in Double-Strand Break Repair." Genetics (2016).

Ferrari, M., Dibitetto, D., De Gregorio, G., Eapen, V.V., Rawal, C.C., Lazzaro, F., Tsabar, M., Marini, F., Haber, J.E., and Pellicioli, A.. "Functional interplay between the 53BP1-ortholog Rad9 and the Mre11 complex regulates resection, end-tethering and repair of a double-strand break.." PLos Genet 11. (2015): e1004928.

Haber, James E. "Deciphering the DNA Damage Response." Cell 162. (2015): 1183-1185.

Haber, James E. "TOPping off meiosis." Mol Cell 57. (2015): 577-581.

Tsabar, M., Eapen, V.V., Mason, J.M., Memisoglu, G., Waterman, D.P., Long, M.J., Bishop, D.K., and Haber, .E.. "Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2." Nucleic Acids Res 43. (2015): 6889-6901.

Tsabar, M., Mason, J.M., Chan, Y.L., Bishop, D.K. and Haber, J.E.. "Caffeine inhibits gene conversion by displacing Rad51 from ssDNA." Nucleic Acids Res 43. (2015): 6902-6918.

Anand, R.P., Tsaponina, O., Greenwell, P.W., Lee, C.S., Du, W., Petes, T.D., and Haber, J.E.. "Chromosome rearrangements via template switching between diverged repeated sequences.." Genes Dev 28. (2014): 2394-2406..

Avsaroglu, B., Bronk, G., Gordon-Messer, S., Ham, J., Bressan, D.A., Haber, J.E., and Kondev, J.. "Effect of chromosome tethering on nuclear organization in yeast.." PLoS ONE 9. (2014): e102474.

Braberg, H., Alexander, R., Shales, M., Xu, J., Franks-Skiba, K.E., Wu, Q., Haber, J.E., and Krogan, N.J.. "Quantitative analysis of triple-mutant genetic interactions.." Nat Protoc 9. (2014): 1867-1881.

Costantino L, Sotiriou SK, Rantala JK, Magin S, Mladenov E, Helleday T, Haber JE, Iliakis G, Kallioniemi OP, Halazonetis TD.. "Break-induced replication repair of damaged forks induces genomic duplications in human cells." Science 343. (6166) (2014): 88-91.

Costantino, L., Sotiriou, S.K., Rantala, J.K., Magin, S., Mladenov, E., Helleday, T., Haber, J.E., Iliakis, G., Kallioniemi, O.P., and Halazonetis, T.D.. "Break-induced replication repair of damaged forks induces genomic duplications in human cells.." Science 243. (2014): 88-91.

Haber, James E. Genome Stability: DNA Repair and Recombination . first ed. New York: Garland Science, 2014.

Lee, C-S and Haber, JE. "Mating-type gene switching in Saccharomyces cerevisiae." Mobile DNA III . Ed. N. Craig and M. Gellert. Washington DC: ASM Press, 2014

Lee, CS, Lee K, Legube G, Haber JE. "Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break.." Nat Struct Mol Biol 21. (1) (2014): 103-109.

Mehta, A and Haber, JE. "Sources of DNA double-strand breaks and models for recombinational DNA repair." Recombination Mechanisms . Ed. S. Kowalczykowski, N. Hunter and W-D Heyer. Cold Spring Harbor Press, NY, 2014

Tsaponina, O., and Haber, J.E.. "Frequent Interchromosomal Template Switches during Gene Conversion in S. cerevisiae.." Mol Cell 55. (2014): 615-625.

Anand RP, Lovett ST, Haber JE. "Break-induced DNA replication." Cold Spring Harb Perspect Biol 5. 12 (2013): a010397.

Dotiwala F, Eapen VV, Harrison JC, Arbel-Eden A, Ranade V, Yoshida S, Haber JE.. "DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase.." Proc Natl Acad Sci USA 110. (1) (2013): E41-49.

Dotiwala, F., Eapen, V.V., Harrison, J.C., Arbel-Eden, A., Ranade, V., Yoshida, S., and Haber, J.E.. "DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase." Proceedings of the National Academy of Sciences of the United States of America 110. (2013): E41-49.

Eapen VV, Haber JE. "DNA damage signaling triggers the cytoplasm-to-vacuole pathway of autophagy to regulate cell cycle progression." Autophagy 9. (3) (2013): 440-441.

Eapen, V.V., and Haber, J.E.. "DNA damage signaling triggers the cytoplasm-to-vacuole pathway of autophagy to regulate cell cycle progression." Autophagy 9. (2013): 440-441.

Haber JE, Braberg H, Wu Q, Alexander R, Haase J, Ryan C, Lipkin-Moore Z, Franks-Skiba KE, Johnson T, Shales M, Lenstra TL, Holstege FC, Johnson JR, Bloom K, Krogan NJ.. "Systematic triple-mutant analysis uncovers functional connectivity between pathways involved in chrosome regulation.." Cell Rep 3. (6) (2013): 2168-2178.

Liebman SW, Haber JE. "Retrospective. Fred Sherman (1932-2013)." Science 342. (6162) (2013): 1059.

Saini N, Ramakrishnan S, Elango R, Ayyar S, Zhang Y, Deem A, Ira G, Haber JE, Lobachev KS, Malkova A.. "Migrating bubble during break-induced replication drives conservative DNA synthesis." Nature 502. (7471) (2013): 389-392.

Sugawara, N., and Haber, J.E.. "Monitoring DNA recombination initiated by HO endonuclease." Methods Mol Biol 920. (2013): 349-370.

Tsabar M, Haber JE. "Chromatin modifications and chromatin remodeling during DNA repair in budding yeast." Curr Opin Genet Dev 23. (2) (2013): 166-173.

Eapen, V.V., Sugawara, N., Tsabar, M., Wu, W.H., and Haber, J.E.. "The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation." Molecular and cellular biology 32. (2012): 4727-4740.

Haber, James E. "Mating-type genes and MAT switching in Saccharomyces cerevisiae." Genetics 191. (2012): 33-64.

Haber, James E. "Mating-type genes and MAT switching in Saccharomyces cerevisiae.." Yeastbook . vol. 191 Ed. A. Hinnebusch. Genetics, 2012. ,33-64.

J Li, E Coïc, K Lee, C-S Lee, Q Wu and Haber, James E. "Regulation of Budding Yeast Mating-Type Switching Donor Preference by the FHA Domain of Fkh1." PLoS Genetics in press. (2012).

Malkova, A and Haber, James E. "Mutations Arising during Recombination." Annu Rev Genet, . vol. 46, 2012. 455-473.

Coïc, E, Marin, J, Kondev, J and Haber, JE. "Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae revealed by donor competition." Genetics 189. 4 (2011): 1225-33.

Hicks, W. M., Yamaguchi, M., Haber, J. E.. "Inaugural Article: Real-time analysis of double-strand DNA break repair by homologous recombination." Proc Natl Acad Sci U S A (2011).

Kim, J. A., Hicks, W. M., Li, J., Tay, S. Y., Haber, J. E.. "Protein phosphatases pph3, ptc2, and ptc3 play redundant roles in DNA double-strand break repair by homologous recombination." Mol Cell Biol 31. 3 (2011): 507-16.

Dotiwala, F., Harrison, J.C., Jain, S., Sugawara, N., and Haber, J.E.. "Mad2 prolongs DNA damage checkpoint arrest caused by a double-strand break via a centromere-dependent mechanism.." Curr Biol. 20. (2010): 328-332.

Hicks, W. M., Kim, M., Haber, J. E.. "Increased mutagenesis and unique mutation signature associated with mitotic gene conversion." Science 329. 5987 (2010): 82-5.

Lydeard, J. R., Lipkin-Moore, Z., Jain, S., Eapen, V. V., Haber, J. E.. "Sgs1 and exo1 redundantly inhibit break-induced replication and de novo telomere addition at broken chromosome ends." PLoS Genet 6. 5 (2010): e1000973.

Lydeard, J. R., Lipkin-Moore, Z., Sheu, Y. J., Stillman, B., Burgers, P. M., Haber, J. E.. "Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly." Genes Dev 24. 11 (2010): 1133-44.

Saponaro, M., Callahan, D., Zheng, X., Krejci, L., Haber, J.E., Klein, H.L., and Liberi, G.. "Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair.." PLoS Genet 6. 2 (2010): e1000858.

Toh, G. W., Sugawara, N., Dong, J., Toth, R., Lee, S. E., Haber, J. E., Rouse, J.. "Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails." DNA Repair (Amst) 9. 6 (2010): 718-26.

Jain, S., Sugawara, N., Lydeard, J., Vaze, M., Tanguy Le Gac, N., Haber, J. E.. "A recombination execution checkpoint regulates the choice of homologous recombination pathway during DNA double-strand break repair." Genes Dev 23. 3 (2009): 291-303.

Kim, J. A., Haber, J. E.. "Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete." Proc Natl Acad Sci U S A 106. 4 (2009): 1151-6.

Prakash, R., Satory, D., Dray, E., Papusha, A., Scheller, J., Kramer, W., Krejci, L., Klein, H., Haber, J. E., Sung, P., Ira, G.. "Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination." Genes Dev 23. 1 (2009): 67-79.

Coic, E., Feldman, T., Landman, A. S., Haber, J. E.. "Mechanisms of Rad52-independent spontaneous and UV-induced mitotic recombination in Saccharomyces cerevisiae." Genetics 179. 1 (2008): 199-211.

Coic, E., Feldman, T., Landman, A. S., Haber, J. E.. "Mechanisms of Rad52-independent spontaneous and UV-induced mitotic recombination in Saccharomyces cerevisiae." Genetics 179. 1 (2008): 199-211.

Coic, E., Feldman, T., Landman, A. S., Haber, J. E.. "Mechanisms of Rad52-independent spontaneous and UV-induced mitotic recombination in Saccharomyces cerevisiae." Genetics 179. 1 (2008): 199-211.

Haber, J. E.. "Alternative endings." Proc Natl Acad Sci U S A 105. 2 (2008): 405-6.

Haber, J. E.. "Evolution of Models of Homologous Recombination." Genome Dynamics and Stability . vol. 3 Ed. Egel, R.. Berlin: Springer-Verlag, 2008. (in press).

Jazayeri, A., Balestrini, A., Garner, E., Haber, J. E., Costanzo, V.. "Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity." Embo J 27. 14 (2008): 1953-62.

Kim, H. S., Vijayakumar, S., Reger, M., Harrison, J. C., Haber, J. E., Weil, C., Petrini, J. H.. "Functional interactions between sae2 and the mre11 complex." Genetics 178. 2 (2008): 711-23.

Cortes-Ledesma, F., de Piccoli, G., Haber, J. E., Aragon, L., Aguilera, A.. "SMC Proteins, new players in the maintenance of genomic stability." Cell Cycle 6. 8 (2007): 914-918.

De Koning, L., Corpet, A., Haber, J. E., Almouzni, G.. "Histone chaperones: an escort network regulating histone traffic." Nat Struct Mol Biol 14. 11 (2007): 997-1007.

Dotiwala, F., Haase, J., Arbel-Eden, A., Bloom, K., Haber, J. E.. "The yeast DNA damage checkpoint proteins control a cytoplasmic response to DNA damage." Proc Natl Acad Sci U S A 104. 27 (2007): 11358-63.

Flott, S., Alabert, C., Toh, G. W., Toth, R., Sugawara, N., Campbell, D. G., Haber, J. E., Pasero, P., Rouse, J.. "Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast." Mol Cell Biol 27. (2007): 6433-45.

Haber, J.E.. "Decisions, decisions: donor preference during budding yeast mating-type switching." Sex in fungi: molecular determination and evolutionary implications . Ed. Heitman, J., Kronstad, J.W., Taylor, J.W., Casselton, L.A.. ASM Press, 2007. 159-170.

Kim, J. A., Kruhlak, M., Dotiwala, F., Nussenzweig, A., Haber, J. E.. "Heterochromatin is refractory to gamma-H2AX modification in yeast and mammals." J Cell Biol 178. 2 (2007): 209-18.

Lydeard, J. R., Jain, S., Yamaguchi, M., Haber, J. E.. "Break-induced replication and telomerase-independent telomere maintenance require Pol32." Nature 448. 7155 (2007): 820-3.

Morrison, A. J., Kim, J. A., Person, M. D., Highland, J., Xiao, J., Wehr, T. S., Hensley, S., Bao, Y., Shen, J., Collins, S. R., Weissman, J. S., Delrow, J., Krogan, N. J., Haber, J. E., Shen, X.. "Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses." Cell 130. 3 (2007): 499-511.

Torres-Rosell, J., De Piccoli, G., Cordon-Preciado, V., Farmer, S., Jarmuz, A., Machin, F., Pasero, P., Lisby, M., Haber, J. E., Aragon, L.. "Anaphase onset before complete DNA replication with intact checkpoint responses." Science 315. 5817 (2007): 1411-5.

Coic, E., Richard, G. F., Haber, J. E.. "Saccharomyces cerevisiae donor preference during mating-type switching is dependent on chromosome architecture and organization." Genetics 173. 3 (2006): 1197-206.

Coic, E., Sun, K., Wu, C., Haber, J. E.. "Cell cycle-dependent regulation of Saccharomyces cerevisiae donor preference during mating-type switching by SBF (Swi4/Swi6) and Fkh1." Mol Cell Biol 26. 14 (2006): 5470-80.

De Piccoli, G., Cortes-Ledesma, F., Ira, G., Torres-Rosell, J., Uhle, S., Farmer, S., Hwang, J. Y., Machin, F., Ceschia, A., McAleenan, A., Cordon-Preciado, V., Clemente-Blanco, A., Vilella-Mitjana, F., Ullal, P., Jarmuz, A., Leitao, B., Bressan, D., D. "Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination." Nat Cell Biol 8. 9 (2006): 1032-4.

Haber, J. E., Debatisse, M.. "Gene amplification: yeast takes a turn." Cell 125. 7 (2006): 1237-40.

Haber, J. E.. "Chromosome breakage and repair." Genetics 173. 3 (2006): 1181-5.

Haber, J. E.. "Transpositions and translocations induced by site-specific double-strand breaks in budding yeast." DNA Repair (Amst) 5. 9-10 (2006): 998-1009.

Harrison, J. C., Haber, J. E.. "Surviving the breakup: the DNA damage checkpoint." Annu Rev Genet 40. (2006): 209-35.

Ira, G., Satory, D., Haber, J. E.. "Conservative inheritance of newly synthesized DNA in double-strand break-induced gene conversion." Mol Cell Biol 26. 24 (2006): 9424-9.

Keogh, M. C., Kim, J. A., Downey, M., Fillingham, J., Chowdhury, D., Harrison, J. C., Onishi, M., Datta, N., Galicia, S., Emili, A., Lieberman, J., Shen, X., Buratowski, S., Haber, J. E., Durocher, D., Greenblatt, J. F., Krogan, N. J.. "A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery." Nature 439. 7075 (2006): 497-501.

McEachern, M. J., Haber, J. E.. "Break-induced replication and recombinational telomere elongation in yeast." Annu Rev Biochem 75. (2006): 111-35.

Sugawara, N., Haber, J. E.. "Repair of DNA double strand breaks: in vivo biochemistry." Methods Enzymol 408. (2006): 416-29.

Valencia-Burton, M., Oki, M., Johnson, J., Seier, T. A., Kamakaka, R., Haber, J. E.. "Different mating-type-regulated genes affect the DNA repair defects of Saccharomyces RAD51, RAD52 and RAD55 mutants." Genetics 174. 1 (2006): 41-55.

Clatworthy, A. E., Valencia-Burton, M. A., Haber, J. E., Oettinger, M. A.. "The MRE11-RAD50-XRS2 complex, in addition to other non-homologous end-joining factors, is required for V(D)J joining in yeast." J Biol Chem 280. 21 (2005): 20247-52.

Corda, Y., Lee, S. E., Guillot, S., Walther, A., Sollier, J., Arbel-Eden, A., Haber, J. E., Geli, V.. "Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by depleting the ribonucleotide reductase inhibitor Sml1 through a pathway controlled by Tel1 kinase and the Mre11 complex." Mol Cell Biol 25. 23 (2005): 10652-64.

Liberi, G., Maffioletti, G., Lucca, C., Chiolo, I., Baryshnikova, A., Cotta-Ramusino, C., Lopes, M., Pellicioli, A., Haber, J. E., Foiani, M.. "Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase." Genes Dev 19. 3 (2005): 339-50.

Malkova, A., Naylor, M. L., Yamaguchi, M., Ira, G., Haber, J. E.. "RAD51-dependent break-induced replication differs in kinetics and checkpoint responses from RAD51-mediated gene conversion." Mol Cell Biol 25. 3 (2005): 933-44.

McEachern, M. J., Haber, J. E.. "Telomerase-independent chromosome maintenance in yeast." Telomeres . Ed. T. de Lange, V. Lundblad, E. Blackburn. Cold Spring Harbor, NY: Cold Spring Harbor Press, 2005

Haber,James E and Wang X. "Role of Saccharomyces Single-Stranded DNA-Binding Protein RPA in the Strand Invasion Step of Double-Strand Break Repair." PLoS Biol. 2. (2004): 104-112.

Haber,James E, Bressan DA, J. Vazquez. "Mating type-dependent constraints on the mobility of the left arm of yeast chromosome III." J. Cell Biol. 164. (2004): 361-371.

Haber,James E, Ira G, Pellicio A, Balijja A, Want X, Fiorani S. Carotenuto W, Liberi G, Bressan D, Wan L,. "DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1." (2004): 1011-7.

Haber,James E, Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S, Carotenuto W, Liberi G, Bressan D, Wan L, Hollingsworth NM, Foiani M. "DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1." Nature 431. (2004): 1011-7.

Haber,James E, Kaye, J. A., Melo, J. A., Cheung, S. K., Vaze, M. B., and Toczyski, D. P.. "DNA breaks promote genomic instability by impeding proper chromosome segregation." Curr Biol 14. (2004): 2096-2106.

Haber,James E, Kaye, J. A., Melo, J.A. Cheung, S. K., Vaze M.B, and Tocayski, D.P.. "DNA breaks promote genomic instability by impeding proper chromosome segregation." Curr. Biol (2004): 2096-2106.

Haber,James E, Lucca C, Vanoli F, Cotta-Ramusino C, Pellicioli A, Liberi G, Foiani M.. "Checkpoint-mediated control of replisome-fork association and signalling in response to replication pausing.." Oncogene Nature 23. (2004): 1206-1213.

Haber,James E, Malkova, A., Swanson, J., German, M., McCusker J.H. Housworth E. A. Stahl, F.W.. "Gene conversion and crossing over along the 405-kb left arm of Saccharomyces cerevisie chromosome VII." Genetics (2004): 49-63.

Haber,James E, Malkova, A., Swanson, J., German, M., McCusker, J. H., Housworth, E. A., Stahl, F. W.. "Gene conversion and crossing over along the 405-kb left arm of Saccharomyces cerevisiae chromosome VII." Genetics 168. (2004): 49-63.

Haber,James E, Miyazaki, T., Bressan, D. A., Shinohara, M., and Shinohara, A.. "In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair." Embo J 23. (2004): 939-949.

Haber,James E, Miyazaki, T., Bressan, D.A. Shinohara, M., and Shinohara. "In vivo assembly and disasembly of Rad52 compleses during double-strand break repair." (2004): 939-949.

Haber,James E, Morrison, A. J., Highland, J., Krogan, N. J., Arbel-Eden, A., Greenblatt, J. F., and Shen, X.. "(2004). INO80 and gamma-H2AX Interaction Links ATP-dependent chromatin remodeling to DNA damage repair." Cell 119. (2004): 767-775.

Haber,James E, Morrison, A.J. Highland, J. Krogan, N.J. Arbel-Eden, A. Greenbalt, J.F and Shen X. "IN080 and gamma-H2AX Interaction Links ATP-dependent chromatin remodeling to DNA damage repair." (2004): 767-775.

Haber,James E, Shroff, R., Arbel-Eden, A. Pilch, D., Ira, G., Bonner, W. M., Petrini, J. and Lichten, M.. "Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break." Curr Biol (2004): 1703-1711.

Haber,James E, Shroff, R., Arbel-Eden, A., Pilch, D., Ira, G., Bonner, W. M., Petrini, J. H., and Lichten, M.. "Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break." Curr Biol 14. (2004): 1703-1711.

Haber,James E, Sugawara, N., Goldfarb, T., Studamire, B., Alani, E.. "Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1." Proc Natl Acad Sci U S A 101. (2004): 9315-9320.

Haber,James E, Unal, E., Arbel-Eden, A., Sattler, U., Shroff, R., Lichten, M., and Koshland, D.. "(2004). DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain." Mol Cell 16. (2004): 991-1002.

Haber,James E, Wang, X., Ira, G., Tercero, J. A., Holmes, A. M., Diffley, J. F.. "Role of DNA replication proteins in double-strand break-induced recombination in Saccharomyces cerevisiae." Mol Cell Biol 24. (2004): 6891-6899.

Haber,James E, Yu J, K. Marshall, M. Yamaguchi and C.F. Weil. "Microhomology-dependent end joining and repair of transposon-induced DNA hairpins by host factors in Saccharomyces cerevisiae." Mol. Cell Biol. 24. (2004): 1351-64.

Haber,James E. "Telomeres thrown for a loop.." (2004).

Haber,James E and Sugawara, N., X. Wang. "In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated homologous recombination." Mol. Cell. 12. (2003): 209-219.

Haber,James E, Clatworthy, A.E., M.A. Valencia, and M.A. Oettinger. "V(D)J Recombination and RAG-Mediated Transposition in Yeast." Mol. Cell 12. (2003): 489-499..

Haber,James E, G. Ira, A. Malkova and N. Sugawara. "Repairing a double-strand chromosome break by homologous recombination: revisiting Robin Hollidays model." Phil. Trans. R. Soc. Lond. 359. (2003): 79-86.

Haber,James E, Ira, G., A. Malkova, G. Liberi, M. Foiani. "Srs2 and Sgs1 ¿Top3 suppress crossovers during double-strand break repair in yeast.." Cell 115. (2003): 401-411.

Haber,James E, Lee, S.E., A. Pellicioli, M.B. Vaze, N. Sugawara, A. Malkova, M. Foiani. "Yeast Rad52 and Rad51 recombination proteins define a second pathway of DNA damage assessment in response to a single double-strand break." Mol. Cell. Biol. 23. (2003).

Haber,James E, Leroy, C. S.E. Lee, M.B. Vaze, F.Ochsenbien, R. Guerois, and M.-C. Marsolier-Kergoat. "(2003) PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break.." Mol. Cell 11. (2003): 1-20.

Haber,James E, Ma, J.-M., E.M. Kim, and S.E. Lee. "Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double strand breaks lacking overlapping end sequences." Mol. Cell. Biol. 23. (2003): 8820-8828.

Haber,James E. "Aging: the sins of the parents." Curr. Biol. 13. (2003): R843-R845.


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