Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51 paralogues with Rad52

Gaines, William A.; Godin, Stephen K.; Kabbinavar, Faiz F.; Rao, Timsi; VanDemark, Andrew P.; Sung, Patrick; Bernstein, Kara A.

doi:10.1038/ncomms8834

Cited by 67 publications

(106 citation statements)

References 45 publications

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“…A recent study showed that these interactions support collaboration between the Shu complex, Rad55–Rad57, and Rad52 to promote Rad51 presynaptic filament assembly in vitro [49]. Such a role is consistent with the epistatic relationship between mutants of Rad55–Rad57 and the Shu complex [48,50,51].…”

Section: The Shu Complex Promotes Rad51 Function In Recombinationasupporting

confidence: 57%

“…Such a role is consistent with the epistatic relationship between mutants of Rad55–Rad57 and the Shu complex [48,50,51]. As Csm2 mutants that affect its interaction with Rad55, but not Psy3 exhibited a null-like phenotype in terms of genotoxic sensitivity and the reduction of Rad51-mediated gene conversion, the Csm2-Rad55 interaction is an important aspect of Shu complex functions [49]. With that said, the Shu complex likely has additional roles.…”

Section: The Shu Complex Promotes Rad51 Function In Recombinationasupporting

confidence: 56%

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Replication-Associated Recombinational Repair: Lessons from Budding Yeast

Bonner

Zhao

2016

Genes

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Recombinational repair processes multiple types of DNA lesions. Though best understood in the repair of DNA breaks, recombinational repair is intimately linked to other situations encountered during replication. As DNA strands are decorated with many types of blocks that impede the replication machinery, a great number of genomic regions cannot be duplicated without the help of recombinational repair. This replication-associated recombinational repair employs both the core recombination proteins used for DNA break repair and the specialized factors that couple replication with repair. Studies from multiple organisms have provided insights into the roles of these specialized factors, with the findings in budding yeast being advanced through use of powerful genetics and methods for detecting DNA replication and repair intermediates. In this review, we summarize recent progress made in this organism, ranging from our understanding of the classical template switch mechanisms to gap filling and replication fork regression pathways. As many of the protein factors and biological principles uncovered in budding yeast are conserved in higher eukaryotes, these findings are crucial for stimulating studies in more complex organisms.

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Section: The Shu Complex Promotes Rad51 Function In Recombinationasupporting

confidence: 57%

Section: The Shu Complex Promotes Rad51 Function In Recombinationasupporting

confidence: 56%

Replication-Associated Recombinational Repair: Lessons from Budding Yeast

Bonner

Zhao

2016

Genes

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“…This increased sensitivity to CPT may suggest that sws-1 plays a more prominent role in the repair of a specific subset of DSB-inducing lesions. The S. cerevisiae Shu complex has been shown in vitro to promote Rad51-mediated repair in concert with Rad52 and the Rad55-Rad57 heterodimer by stimulating Rad51 loading onto ssDNA and stabilizing it thereafter (Gaines et al 2015). Further studies in S. cerevisiae suggest that the Shu complex promotes Rad51 assembly on meiotic chromosomes in vivo based on a reduced number of Rad51 foci in Shu complex mutants (Sasanuma et al 2013).…”

Section: Sws-1 Mutants Are Sensitive To Genotoxins That Induce Hr Submentioning

confidence: 99%

“…Much of our understanding of the RAD51 paralogs comes from studies in budding yeast in which the Rad51 paralogs form two subcomplexes, the Shu complex (also called the PCSS complex) and the Rad55-Rad57 complex. The Shu complex is an obligate hetero-tetramer composed of Psy3, Csm2, Shu1, and Shu2, which facilitates HR-mediated DSB repair by stimulating Rad51 filament formation (Shor et al 2005;Mankouri et al 2007;Ball et al 2009;Godin et al 2013Godin et al , 2015Hong and Kim 2013;Sasanuma et al 2013;Gaines et al 2015). Csm2 and Psy3 are Rad51 paralogs whereas Shu2 is a member of the SWS1 protein family, defined by a highly conserved SWIM domain (Makarova et al 2002;Martin et al 2006;Godin et al 2015).…”

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confidence: 99%

Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans

et al. 2016

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Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast. Evolutionary analysis of the SWIM domain identified Caenorhabditis elegans sws-1 as a putative homolog of the yeast Shu complex member Shu2. Using a CRISPR-induced nonsense allele of sws-1, we show that sws-1 promotes HR in mitotic and meiotic nuclei. sws-1 mutants exhibit sensitivity to DSBinducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. Phenotypic similarities between sws-1 and the two RAD-51 paralogs rfs-1 and rip-1 suggest that they function together. Indeed, we detect direct interaction between SWS-1 and RIP-1 by yeast two-hybrid assay that is mediated by the SWIM domain in SWS-1 and the Walker B motif in RIP-1. Furthermore, RIP-1 bridges an interaction between SWS-1 and RFS-1, suggesting that RIP-1 facilitates complex formation with SWS-1 and RFS-1. We propose that SWS-1, RIP-1, and RFS-1 compose a C. elegans Shu complex. Our work provides a new model for studying Shu complex disruption in the context of a multicellular organism that has important implications as to why mutations in the human RAD51 paralogs are associated with genome instability.KEYWORDS homologous recombination; RAD51 paralog; Shu complex; camptothecin; helq-1 D NA double-strand breaks (DSBs) are extremely cytotoxic lesions that threaten genome integrity. DSBs arise from both endogenous sources, such as replicative damage, or exogenous sources, such as ionizing radiation (IR) and chemotherapeutic agents. To ensure the maintenance of the genome, DSBs need to be repaired by high-fidelity repair pathways, the most robust of which is homologous recombination (HR), in which DNA from a sister chromatid or homologous chromosome provides a repair template. Initial processing of DSB ends by resection forms 39 singlestranded DNA (ssDNA) overhangs that are coated with the ssDNA-binding protein RPA. The exchange of RPA for the recombinase enzyme RAD51 facilitates the homology search and strand invasion of homologous DNA templates to form displacement loop structures. Subsequent stabilization of HR intermediates then requires removal of RAD51 from the doublestranded DNA to allow access to the DNA polymerization machinery. Given the central role of the RAD51 filament in HR, its assembly and disassembly are tightly regulated to ensure the fidelity of repair (Krejci et al. 2012;Jasin and Rothstein 2013;Heyer 2015).Key mediators of RAD51 filament assembly are the RAD51 paralogs. In humans, there are six RAD51 paralogs: RAD51B, RAD51C, RA...

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“…After capture of the second end of the DSB and strand extension, RAD52 anneals RPA-coated ssDNA. 7,[10][11][12] The heterozygous P183S mutation lies in the ssDNA annealing domain, and our assays suggest that ssDNA annealing of haematologica 2017; 102:e71 CASE REPORT …”

mentioning

confidence: 99%