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Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans.
- Source :
-
Genetics [Genetics] 2016 May; Vol. 203 (1), pp. 133-45. Date of Electronic Publication: 2016 Mar 02. - Publication Year :
- 2016
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Abstract
- 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 DSB-inducing 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.<br /> (Copyright © 2016 by the Genetics Society of America.)
- Subjects :
- Animals
CRISPR-Cas Systems
Caenorhabditis elegans Proteins chemistry
Caenorhabditis elegans Proteins genetics
Carrier Proteins metabolism
Cell Line
Gene Expression
Gene Order
Genetic Loci
Germ-Line Mutation
Multiprotein Complexes metabolism
Mutagens toxicity
Mutation
Protein Binding
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Rad51 Recombinase genetics
Recombinational DNA Repair drug effects
Caenorhabditis elegans genetics
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins metabolism
Homologous Recombination
Rad51 Recombinase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1943-2631
- Volume :
- 203
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 26936927
- Full Text :
- https://doi.org/10.1534/genetics.115.185827