RRC ID 46395
Author Lemmens BB, Johnson NM, Tijsterman M.
Title COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.
Journal PLoS Genet.
Abstract Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs). DSBs can be repaired via homologous recombination (HR) or non-homologous end joining (NHEJ), yet only repair via HR can generate the interhomolog crossovers (COs) needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.
Volume 9(2)
Pages e1003276
Published 2013
DOI 10.1371/journal.pgen.1003276
PMID 23408909
PMC PMC3567172
MeSH Animals Antigens, Nuclear / genetics Antigens, Nuclear / metabolism Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / genetics* Chromosome Segregation / genetics Crossing Over, Genetic DNA Breaks, Double-Stranded DNA End-Joining Repair / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Endodeoxyribonucleases / genetics Endodeoxyribonucleases / metabolism Germ Cells / metabolism Homologous Recombination / genetics* Ku Autoantigen Meiosis / genetics* Pachytene Stage / genetics
IF 5.224
Times Cited 21
C.elegans tm1524 tm1842 tm1145