COM-1 Promotes Homologous Recombination during Caenorhabditis elegans Meiosis by Antagonizing Ku-Mediated Non-Homologous End Joining

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. © 2013 lemmens et al.