Rad52 and Rad59 exhibit both overlapping and distinct functions

Feng, Q.; Düring, Louis; Mayolo, Adriana Antúnez de; Lettier, Gaëlle; Lisby, Michael; Erdeniz, Naz; Mortensen, Uffe Hasbro; Rothstein, Rodney

doi:10.1016/j.dnarep.2006.08.007

Cited by 34 publications

(37 citation statements)

References 43 publications

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“…Rad22 shows 35% similarity and 24% identity with Rad52 of S. cerevisiae, while Rti1 shows 32 and 19%, respectively (supplemental Figure A1). Both fission yeast proteins display significant homology to Rad59, but unlike Rad59, both carry a C-terminal domain for interaction with Rad51 (Bai and Symington 1996;van den Bosch et al 2002;Feng et al 2007). Conservation is strongest in the Nterminal region, which contains the Rad52/22 homology domain common to all members of the RAD52 superfamily (Iyer et al 2002), whereas the C-terminal ends of the proteins show more variability (Figure 1 and supplemental Figure A1).…”

Section: Resultsmentioning

confidence: 99%

The Rad52 Homologs Rad22 and Rti1 ofSchizosaccharomyces pombeAre Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

et al. 2008

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Proteins of the RAD52 epistasis group play an essential role in repair of some types of DNA damage and genetic recombination. In Schizosaccharomyces pombe, Rad22 (a Rad52 ortholog) has been shown to be as necessary for repair and recombination events during vegetative growth as its Saccharomyces cerevisiae counterpart. This finding contrasts with previous reports where, due to suppressor mutations in the fbh1 gene, rad22 mutants did not display a severe defect. We have analyzed the roles of Rad22 and Rti1, another Rad52 homolog, during meiotic recombination and meiosis in general. Both proteins play an important role in spore viability. During meiotic prophase I, they partially colocalize and partially localize to Rad51 foci and linear elements. Genetic analysis showed that meiotic interchromosomal crossover and conversion events were unexpectedly not much affected by deletion of either or both genes. A strong decrease of intrachromosomal recombination assayed by a gene duplication construct was observed. Therefore, we propose that the most important function of Rad22 and Rti1 in S. pombe meiosis is repair of double-strand breaks with involvement of the sister chromatids. In addition, a novel mating-type-related repair function of Rad22 specific to meiosis and spore germination is described.

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Section: Resultsmentioning

confidence: 99%

The Rad52 Homologs Rad22 and Rti1 ofSchizosaccharomyces pombeAre Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

et al. 2008

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“…However, differences in the biochemical characteristics of the Rad52 and Rad59 proteins [35], and the genetic characteristics of the rad52 and rad59 mutants [82] suggest that they are paralogs. Our genetic results support this as the rad52 rad59 double mutant is more defective for DSB-stimulated translocation than either single mutant, particularly when the 60 bp substrates are used (Table 3).…”

Section: Discussionmentioning

confidence: 99%

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

2008

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Exposure to ionizing radiation results in a variety of genome rearrangements that have been linked to tumor formation. Many of these rearrangements are thought to arise from the repair of doublestrand breaks (DSBs) by several mechanisms, including homologous recombination (HR) between repetitive sequences dispersed throughout the genome. Doses of radiation sufficient to create DSBs in or near multiple repetitive elements simultaneously could initiate single-strand annealing (SSA), a highly-efficient, though mutagenic, mode of DSB repair. We have investigated the genetic control of the formation of translocations that occur spontaneously and those that form after the generation of DSBs adjacent to homologous sequences on two, non-homologous chromosomes in Saccharomyces cerevisiae. We found that mutations in a variety of DNA repair genes have distinct effects on break-stimulated translocation. Furthermore, the genetic requirements for repair using 300 bp and 60 bp recombination substrates were different, suggesting that the SSA apparatus may be altered in response to changing substrate lengths. Notably, RAD59 was found to play a particularly significant role in recombination between the short substrates that was partially independent of that of RAD52. The high frequency of these events suggests that SSA may be an important mechanism of genome rearrangement following acute radiation exposure.

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“…Vectors, expressing C-terminally YFP-tagged Rad52 species containing alanine substitution mutations, were derivatives of the CEN-based plasmid, pWJ1213 (26), harboring RAD52 fused to YFP and a HIS3 marker for selection. Specifically, the polylinker of pWJ1213 was removed by a blunt end ligation of ends obtained by cutting pWJ1213 with SacI, followed by removal of the 3Ј-overhang by T4 polymerase and with XmaI, where the 5Ј-overhang was filled in by T4 polymerase, to produce the plasmid pWJ1213-⌬XmaI-SacI.…”

Section: Methodsmentioning

confidence: 99%

Interaction with RPA Is Necessary for Rad52 Repair Center Formation and for Its Mediator Activity

Plate

Hallwyl

Shi

et al. 2008

Journal of Biological Chemistry

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Homologous recombination (HR) is a major DNA repair pathway and therefore essential for maintaining the integrity of the genome. HR is catalyzed by proteins encoded by genes of the RAD52 epistasis group, including the recombinase Rad51 and its mediator Rad52. HR proteins fused with green fluorescent protein form foci at damaged DNA reflecting the assembly of repair centers that harbor a high concentration of repair proteins. Rad52 mediates the recruitment of Rad51 and other HR proteins to DNA damage. To understand the mechanism for the assembly of Rad52-dependent DNA repair centers, we used a mutational strategy to identify a Rad52 domain essential for its recruitment to DNA repair foci. We present evidence to implicate an acidic domain in Rad52 in DNA repair focus formation. Mutations in this domain confer marked DNA damage sensitivity and recombination deficiency. Importantly, these Rad52 mutants are specifically compromised for interaction with the single-stranded DNA-binding factor RPA. Based on these findings, we propose a model where Rad52 displaces RPA from single-stranded DNA using the acidic domain as a molecular lever.In eukaryotes, DNA double strand break (DSB) 4 repair is essential for maintaining genetic stability. The major pathway of DSB repair in the yeast Saccharomyces cerevisiae is homologous recombination (HR), and the evolutionarily conserved proteins involved in this process are encoded by members of the RAD52 epistasis group, including RAD50, RAD51, RAD52, RAD54, RAD55, RAD57, RAD59, RDH54/TID1, RFA1, MRE11, and XRS2 (1). In mitotic cells, most DSBs are eliminated by the synthesis-dependent strand annealing pathway of HR (2). The first step of this pathway involves resection of the ends at the DSB to produce a pair of 3Ј-single-stranded tails. Subsequently, one of these single-stranded tails invades an intact homologous double-stranded DNA sequence to produce a D-loop. DNA polymerase extends the invading end, hence acquiring DNA information that is complementary to the noninvading end. At this stage, the invading strand is dissociated from the invaded duplex and anneals to the noninvading end of the break. Repair is completed when the break is sealed via additional DNA synthesis and ligation.In vitro it has been shown that Rad51 can catalyze the DNA strand invasion reaction via a filamentous intermediate called the presynaptic filament (3, 4). The efficiency of this reaction is dependent on several accessory factors, including the heterotrimeric single-stranded DNA-binding protein RPA (3, 5-7). RPA minimizes intramolecular secondary structure in the singlestranded DNA (ssDNA) that would otherwise impede presynaptic filament assembly. Paradoxically, if an amount of RPA sufficient to saturate the ssDNA is added to the in vitro recombination reaction prior to or together with Rad51, it strongly inhibits strand invasion by limiting access of Rad51 to the ssDNA (1, 8). Chromatin immunoprecipitation and cytological studies have also shown that RPA excludes Rad51 from the HR substrate (9, 10 -13...

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Rad52 and Rad59 exhibit both overlapping and distinct functions

Cited by 34 publications

References 43 publications

The Rad52 Homologs Rad22 and Rti1 ofSchizosaccharomyces pombeAre Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

The Rad52 Homologs Rad22 and Rti1 ofSchizosaccharomyces pombeAre Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

Interaction with RPA Is Necessary for Rad52 Repair Center Formation and for Its Mediator Activity

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