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Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs

Proceedings of the National Academy of Sciences - PNAS, 2018-05, Vol.115 (19), p.E4443-E4452 [Peer Reviewed Journal]

Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles ;Copyright National Academy of Sciences May 8, 2018 ;2018 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1719029115 ;PMID: 29686104

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Title:
Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs
Author: Girard, Chloe ; Roelens, Baptiste ; Zawadzki, Karl A. ; Villeneuve, Anne M.
Subjects: Animals ; Biological Sciences ; Breakage ; Caenorhabditis elegans ; Caenorhabditis elegans - embryology ; Caenorhabditis elegans - genetics ; Caenorhabditis elegans Proteins - genetics ; Caenorhabditis elegans Proteins - metabolism ; Cell division ; Chromosomes ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA repair ; Embryo, Nonmammalian - cytology ; Embryo, Nonmammalian - metabolism ; Genetic crosses ; Genomes ; Genotype & phenotype ; Heredity ; Homologous Recombination ; Homology ; Lethality ; Meiosis ; MRE11 protein ; Nijmegen breakage syndrome ; Non-homologous end joining ; Phenotypes ; PNAS Plus ; Progeny ; Prophase ; Proteins ; Recombinase ; Reproduction (biology) ; Restoration ; Sexual reproduction ; Worms
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2018-05, Vol.115 (19), p.E4443-E4452
Description: Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the Caenorhabditis elegans ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Loss of nbs-1 leads to severely reduced loading of recombinase RAD-51, ssDNA binding protein RPA, and pro-crossover factor COSA-1 during meiotic prophase progression; aggregated and fragmented chromosomes at the end of meiotic prophase; and 100% progeny lethality. These phenotypes reflect a role for NBS-1 in processing of meiotic DSBs for HR that is shared with its interacting partners MRE-11-RAD-50 and COM-1 (ortholog of Com1/Sae2/CtIP). Unexpectedly, in contrast to MRE-11 and RAD-50, NBS-1 is not required for meiotic DSB formation. Meiotic defects of the nbs-1 mutant are partially suppressed by abrogation of the nonhomologous end-joining (NHEJ) pathway, indicating a role for NBS-1 in antagonizing NHEJ during meiosis. Our data further reveal that NBS-1 and COM-1 play distinct roles in promoting HR and antagonizing NHEJ. We propose a model in which different components of the MRN-C complex work together to couple meiotic DSB formation with efficient and timely engagement of HR, thereby ensuring crossover formation and restoration of genome integrity before the meiotic divisions.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.1719029115
PMID: 29686104
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs

Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles ;Copyright National Academy of Sciences May 8, 2018 ;2018 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1719029115 ;PMID: 29686104

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