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Journal ArticleDOI

Rad51 Protein Controls Rad52-mediated DNA Annealing

23 May 2008-Journal of Biological Chemistry (American Society for Biochemistry and Molecular Biology)-Vol. 283, Iss: 21, pp 14883-14892
TL;DR: Regulation of Rad52-mediated annealing suggests a control function for Rad51 in deciding the recombination path taken for a processed DNA break; the ssDNA can be directed to either Rad51-mediated DNA strand invasion or to Rad 52- mediated DNA annealed.
About: This article is published in Journal of Biological Chemistry.The article was published on 2008-05-23 and is currently open access. It has received 93 citations till now. The article focuses on the topics: Replication protein A & Strand invasion.
Citations
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: 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.

1,080 citations


Cites background from "Rad51 Protein Controls Rad52-mediat..."

  • ...For example, Rad51 prevents Rad52-mediated annealing of complementary ssDNA in yeast [91,92], and RAD51 inhibition in mammalian cells upregulates RAD52-mediated SSA activity [17]....

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Journal ArticleDOI
TL;DR: The factors and mechanistic stages of recombination that are subject to regulation are reviewed and it is suggested that recombination achieves flexibility and robustness by proceeding through metastable, reversible intermediates.
Abstract: Homologous recombination (HR) is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage, including DNA double-strand breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks, enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and elevated cancer predisposition, demonstrating a clear cellular need for recombination. However, recombination can also lead to genome rearrangements. Unrestrained recombination causes undesired endpoints (translocation, deletion, inversion) and the accumulation of toxic recombination intermediates. Evidently, HR must be carefully regulated to match specific cellular needs. Here, we review the factors and mechanistic stages of recombination that are subject to regulation and suggest that recombination achieves fle...

971 citations


Cites background from "Rad51 Protein Controls Rad52-mediat..."

  • ...BLM may also contribute to a noncrossover outcome by promoting the SDSA pathway, as indicated by genetic studies in Drosophila (3)....

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  • ...SDSA, which does not have these deleterious consequences, is the favored subpathway (123)....

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  • ...In the presence of a second end, the predominant pathway for DSB repair in somatic cells appears to be synthesis-dependent strand annealing (SDSA), in which the extended D-loop is reversed, leading to annealing of the newly synthesized strand with the resected strand of the second end (Figure 1) (123)....

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  • ...The DNA damage sensitivity profile of RTEL1 mutants is more consistent with a defect in HR, suggesting that RTEL1 may play a role in SDSA (169)....

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  • ...F or p er so na l u se o nl y. Displacement loop (D-loop): primary DNA-strand invasion product of the Rad51-ssDNA filament leading to the different HR subpathways (BIR, SDSA, dHJ) Break-induced replication (BIR): a subpathway of HR where a single-ended DSB invades and establishes a fullfledged replication fork Holliday junction (HJ): Cross-stranded joint molecule HR intermediate Synthesis-dependent strand annealing (SDSA): a subpathway of HR where the second end of the DSB anneals with the extended strand of the first end Double Holliday junction (dHJ): HR intermediate leading to crossovers....

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Journal ArticleDOI
TL;DR: It is proposed that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR) that will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication.
Abstract: Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV). A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2–5 base pairs (bp). Third, endpoints occur near pre-existing low copy repeats (LCRs). Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR) for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR). Under these circumstances, single-strand 3′ tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication.

763 citations


Cites background from "Rad51 Protein Controls Rad52-mediat..."

  • ...We suggest that annealing is catalyzed by Rad52....

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  • ...Rad52 is essential for the single-strand annealing reaction that PLoS Genetics | www.plosgenetics.org 6 January 2009 | Volume 5 | Issue 1 | e1000327 deletes sequence between direct repeats [96], and it anneals single strands in vitro [97]....

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  • ...These observations show that microhomology junction formation can be mediated by a different protein in yeast, as well as by Rad52....

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  • ...In one of these cases, frequent switches were associated with microhomology junctions in a Rad51-independent, Rad52-dependent process that produced translocations and inversions at sites of highly diverged genes [66]....

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  • ...In vitro, Rad51 inhibits the single-strand annealing activity of Rad52 [99], suggesting that the absence of Rad51 might exercise tight control of the switch from strand invasion to annealing of single strands....

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01 Jan 1996

510 citations

References
More filters
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: This review encompasses different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.
Abstract: The budding yeast Saccharomyces cerevisiae has been the principal organism used in experiments to examine genetic recombination in eukaryotes. Studies over the past decade have shown that meiotic recombination and probably most mitotic recombination arise from the repair of double-strand breaks (DSBs). There are multiple pathways by which such DSBs can be repaired, including several homologous recombination pathways and still other nonhomologous mechanisms. Our understanding has also been greatly enriched by the characterization of many proteins involved in recombination and by insights that link aspects of DNA repair to chromosome replication. New molecular models of DSB-induced gene conversion are presented. This review encompasses these different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.

2,175 citations

Journal ArticleDOI
TL;DR: An overview of recent biochemical and structural analyses of the Rad52 group proteins is provided and how this information can be incorporated into genetic studies of recombination is discussed.
Abstract: The process of homologous recombination is a major DNA repair pathway that operates on DNA double-strand breaks, and possibly other kinds of DNA lesions, to promote error-free repair. Central to the process of homologous recombination are the RAD52 group genes (RAD50, RAD51, RAD52, RAD54, RDH54/TID1, RAD55, RAD57, RAD59, MRE11, and XRS2), most of which were identified by their requirement for the repair of ionizing-radiation-induced DNA damage in Saccharomyces cerevisiae. The Rad52 group proteins are highly conserved among eukaryotes, and Rad51, Mre11, and Rad50 are also conserved in prokaryotes and archaea. Recent studies showing defects in homologous recombination and double-strand break repair in several human cancer-prone syndromes have emphasized the importance of this repair pathway in maintaining genome integrity. Although sensitivity to ionizing radiation is a universal feature of rad52 group mutants, the mutants show considerable heterogeneity in different assays for recombinational repair of double-strand breaks and spontaneous mitotic recombination. Herein, I provide an overview of recent biochemical and structural analyses of the Rad52 group proteins and discuss how this information can be incorporated into genetic studies of recombination.

1,012 citations

Journal ArticleDOI
17 Sep 2004-Cell
TL;DR: The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.

938 citations

Journal ArticleDOI
15 May 2003-Nature
TL;DR: The role of SRS2 in recombination modulation is clarified by purifying its encoded product and examining its interactions with the Rad51 recombinase, and it is shown that Srs2 acts by dislodging Rad51 from ssDNA.
Abstract: Mutations in the Saccharomyces cerevisiae gene SRS2 result in the yeast's sensitivity to genotoxic agents, failure to recover or adapt from DNA damage checkpoint-mediated cell cycle arrest, slow growth, chromosome loss, and hyper-recombination1,2. Furthermore, double mutant strains, with mutations in DNA helicase genes SRS2 and SGS1, show low viability that can be overcome by inactivating recombination, implying that untimely recombination is the cause of growth impairment1,3,4. Here we clarify the role of SRS2 in recombination modulation by purifying its encoded product and examining its interactions with the Rad51 recombinase. Srs2 has a robust ATPase activity that is dependent on single-stranded DNA (ssDNA) and binds Rad51, but the addition of a catalytic quantity of Srs2 to Rad51-mediated recombination reactions causes severe inhibition of these reactions. We show that Srs2 acts by dislodging Rad51 from ssDNA. Thus, the attenuation of recombination efficiency by Srs2 stems primarily from its ability to dismantle the Rad51 presynaptic filament efficiently. Our findings have implications for the basis of Bloom's and Werner's syndromes, which are caused by mutations in DNA helicases and are characterized by increased frequencies of recombination and a predisposition to cancers and accelerated ageing5.

609 citations