Rad54: the Swiss Army knife of homologous recombination?

Heyer, Wolf Dietrich; Li, Xuan; Rolfsmeier, Michael; Zhang, Xiaoping

doi:10.1093/nar/gkl481

Cited by 227 publications

(250 citation statements)

References 111 publications

(158 reference statements)

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“…In particular, we analysed the effect of rad54 deletion in the mph1 background in terms of DNA damage sensitivity and spontaneous mutation rate. RAD54 codes for a dsDNA-dependent ATPase considered a key factor of HR, probably acting at multiple stages in concert with Rad51 (Heyer et al, 2006). Similarly to the HR mutants we have previously tested (Schürer et al, 2004), rad54 is epistatic to mph1 in terms of DNA damage sensitivity.…”

Section: Genetic Interactions Of Rad54 and Mms4-mus81 With Mph1mentioning

confidence: 83%

“…ssDNA is initially bound by the RPA protein, hence Rad51 assembles on RPAcoated ssDNA to form the presynaptic filament, where Rad52 and the Rad55-Rad57 heterodimer are required as cofactors (reviewed in Krogh and Symington, 2004). In addition, the Rad54 protein is required at several steps (for review, see Heyer et al, 2006). HR may assist replication fork progression in the presence of DNA damage (Oakley and Hickson, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Panico

Ede

Schildmann

et al. 2009

Yeast

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In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result -depending on the genetic background -in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57 ) and in the DNA damage checkpoint (rad9, rad24, rad17 ). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.

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Section: Genetic Interactions Of Rad54 and Mms4-mus81 With Mph1mentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Panico

Ede

Schildmann

et al. 2009

Yeast

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“…Rad51 catalyzes the early strand invasion step of HRR, whereas Rad54 likely acts at multiple stages during HRR (reviewed in Sung et al, 2003;Tan et al, 2003;Heyer et al, 2006). However, Rad54 probably acts alongside Rad51 early in HRR, because Rad54 stimulates Rad51 in DNA pairing reactions (Petukhova et al, 1998;Zhang et al, 2007).…”

Section: Shu1 Functions In Rad51-and Rad54-dependent Homologous Recommentioning

confidence: 99%

Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3

Mankouri

Ngo

Hickson

2007

MBoC

125

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CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination repair (HRR), their precise role(s) within this pathway remains poorly understood. Here, we have identified a specific role for the Shu proteins in a Rad51/Rad54-dependent HRR pathway(s) to repair MMS-induced lesions during S-phase. We show that, although mutation of RAD51 or RAD54 prevented the formation of MMS-induced HRR intermediates (X-molecules) arising during replication in sgs1 cells, mutation of SHU genes attenuated the level of these structures. Similar findings were also observed in shu1 cells in which Rmi1 or Top3 function was impaired. We propose a model in which the Shu proteins act in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex. INTRODUCTIONHomologous recombination repair (HRR) is a well-conserved cellular process for the repair of single-strand DNA (ssDNA) gaps and double-strand DNA breaks (DSBs) that can arise during DNA synthesis or as a result of replication fork stalling during S-phase. Although many of the key proteins involved in HRR have been identified (reviewed in Paques and Haber, 1999;Sung et al., 2003;West, 2003;Krogh and Symington, 2004), in some cases their precise function(s) remains to be identified. Moreover, the mechanisms for suppression of inappropriate HRR in S-phase are only poorly defined. It is likely that HRR must be carefully regulated and/or executed in dividing cells, as inappropriate or excessive HR can lead to genome rearrangements and cancer in mammals. This is exemplified by the cancer-predisposition disorder, Bloom's syndrome, which is caused by mutation in the human BLM gene (reviewed in German, 1993). Because the BLM protein, in conjunction with its associated proteins, hTOPOIII␣ and hRMI1 (Johnson et al., 2000;Wu et al., 2000;Yin et al., 2005), can catalyze dissolution of HRR intermediates in vitro Plank et al., 2006;Raynard et al., 2006;Wu et al., 2006), it is likely that unprocessed and/or aberrantly processed HRR intermediates at least partly contribute to the cellular defects in Bloom's syndrome. Indeed, Bloom's syndrome cells classically demonstrate elevated levels of sister chromatid exchanges, mitotic recombination, and genome instability. Mutation of the BLM, hTOPOIII␣, or hRMI1 homologues in Saccharomyces cerevisiae (SGS1, TOP3, or RMI1, respectively) similarly causes sensitivity to genotoxic agents, hyper-recombination, and synthetic lethality with mutations in other genes also implicated in HRR (e.g., MUS81 and SRS2; Gangloff et al., 1994;Watt et al., 1996;Gangloff et al., 2000;Mullen et al., 2001;Fabre et al., 2002;Chang et al., 2005;Mullen et al., 2005). Furthermore, unresolved HRR intermediates have been directly visualized by two-dimensional (2D) gel electrophoresis in cells lacking Sgs1 or in cells w...

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“…Homology-directed repair initially involves an Mre11-Rad50-Nbs1 (MRN)-mediated 5 0 -3 0 resection followed by Rad51-mediated homology search and strand invasion. The Rad51 recombinase functions in concert with a series of other factors including the Rad51 paralogs (Xrcc2, Xrcc3, RAD51L1, RAD51L2, RAD51L3), Rad52 and Rad54 proteins to promote strand invasion and subsequent recombination (West, 2003;Thacker and Zdzienicka, 2004;Wyman et al, 2004;Heyer et al, 2006;Helleday et al, 2007). Strand invasion and migration involves formation of a structure termed a Holliday Junction, resolution of which via Rad54, Mus81/Emc1 and Rad51C/Xrcc3 occurs following repair synthesis by DNA polymerase to complete the repair process.…”

Section: Introductionmentioning

confidence: 99%

DNA double-strand break repair and development

Phillips

McKinnon

2007

Oncogene

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Normal development of an organism requires the ability to respond to DNA damage. A particularly deleterious lesion is a DNA double-strand break (DSB). The cellular response to DNA DSBs occurs via an integrated sensing and signaling network that maintains genomic stability. The outcomes of defective DNA DSB repair are related to the developmental stage of an organism, and often show striking tissue specificity. Many human diseases are associated with deficiencies in DNA DSB repair and can be characterized by neuropathology, immune deficiency, growth retardation or predisposition to cancer. This review will focus on the requirements of the DNA DSB response that function to maintain homeostasis during mammalian development.

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Rad54: the Swiss Army knife of homologous recombination?

Cited by 227 publications

References 111 publications

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3

DNA double-strand break repair and development

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