Homologous recombination in DNA repair and DNA damage tolerance

Li, Xuan; Heyer, Wolf Dietrich

doi:10.1038/cr.2008.1

Cited by 952 publications

(776 citation statements)

References 163 publications

(214 reference statements)

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“…DNA damage in template DNA during replication can be deleterious to a cell, since it may cause replication fork blockage or collapse (Li and Heyer, 2008). Cell survival in the presence of replicative stress requires S-phase checkpoint and DNA repair functions (Nyberg et al, 2002;Friedberg, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…These mechanisms cannot operate during replication, where the two parental strands are separated (Friedberg, 2003). Tolerance of replication blocking lesions requires alternative mechanisms, such as translesion DNA synthesis (TLS), a generally deemed error-prone bypass process and fork regression or homologous recombination (HR), allowing error-free bypass of replication-blocking lesions (Ulrich, 2005;Li and Heyer, 2008). Recently, also repriming on the leading strand has been discussed as a potential errorfree mechanism (Lopes et al, 2006).…”

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: Introductionmentioning

confidence: 99%

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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“…4 RAD51 protein promotes homology search and strand invasion during HRR, which uses an undamaged copy of broken DNA as a template for the repair process. 5 Homologous recombination repair events are also regulated by RAD51 paralogs, RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3. 6 The paralogs can form various complexes in human cells displaying different functions during HRR.…”

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confidence: 99%

BCR/ABL kinase interacts with and phosphorylates the RAD51 paralog, RAD51B

et al. 2009

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“…To maintain such genetic integrity, cells have evolved elaborate mechanisms such as base excision repair (BER; Hegde et al, 2008), nucleotide excision repair (NER; Shuck et al, 2008), homologous recombination (HR; Li and Heyer, 2008) repair, and nonhomologous end joining (Weterings and Chen, 2008) pathways to repair diverse types of DNA damage. To allow for variation, however, organisms utilize meiosis to shuffle genetic material so as to increase genetic diversity in populations and in the species.…”

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Replication Protein A (RPA1a) Is Required for Meiotic and Somatic DNA Repair But Is Dispensable for DNA Replication and Homologous Recombination in Rice

et al. 2009

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Replication protein A (RPA), a highly conserved single-stranded DNA-binding protein in eukaryotes, is a stable complex comprising three subunits termed RPA1, RPA2, and RPA3. RPA is required for multiple processes in DNA metabolism such as replication, repair, and homologous recombination in yeast (Saccharomyces cerevisiae) and human. Most eukaryotic organisms, including fungi, insects, and vertebrates, have only a single RPA gene that encodes each RPA subunit. Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), however, possess multiple copies of an RPA gene. Rice has three paralogs each of RPA1 and RPA2, and one for RPA3. Previous studies have established their biochemical interactions in vitro and in vivo, but little is known about their exact function in rice. We examined the function of OsRPA1a in rice using a T-DNA insertional mutant. The osrpa1a mutants had a normal phenotype during vegetative growth but were sterile at the reproductive stage. Cytological examination confirmed that no embryo sac formed in female meiocytes and that abnormal chromosomal fragmentation occurred in male meiocytes after anaphase I. Compared with wild type, the osrpa1a mutant showed no visible defects in mitosis and chromosome pairing and synapsis during meiosis. In addition, the osrpa1a mutant was hypersensitive to ultraviolet-C irradiation and the DNA-damaging agents mitomycin C and methyl methanesulfonate. Thus, our data suggest that OsRPA1a plays an essential role in DNA repair but may not participate in, or at least is dispensable for, DNA replication and homologous recombination in rice.

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Homologous recombination in DNA repair and DNA damage tolerance

Cited by 952 publications

References 163 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

BCR/ABL kinase interacts with and phosphorylates the RAD51 paralog, RAD51B

Replication Protein A (RPA1a) Is Required for Meiotic and Somatic DNA Repair But Is Dispensable for DNA Replication and Homologous Recombination in Rice

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