TY - JOUR T1 - COM-1 Promotes Homologous Recombination during Caenorhabditis elegans Meiosis by Antagonizing Ku-Mediated Non-Homologous End Joining A1 - Lemmens, Bennie B. L. G. A1 - Johnson, Nicholas M. A1 - Tijsterman, Marcel Y1 - 2013/02/07 N2 - Author Summary Sexually reproducing animals create germ cells via meiosis, a cell division program that requires the induction and faithful repair of DNA double-strand breaks (DSBs). Meiotic DSBs are typically repaired via homologous recombination (HR), an error-free repair pathway that generates transient links between homologous chromosomes, named crossovers (COs), which are needed for proper chromosome segregation. To date, it is unclear how germ cells channel these programmed DSBs into HR and not into error-prone DSB repair pathways such as non-homologous end joining (NHEJ). We used the genetically tractable animal model Caenorhabditis elegans to study the mechanisms underlying the strong HR bias in germ cells. Here, we identify COM-1, the worm homolog of CtIP, as a crucial regulator of meiotic DSB repair pathway choice: COM-1 effectively blocks the action of the NHEJ complex Ku, thereby assuring correct repair via HR. In addition, we show that unscheduled NHEJ activity during meiosis leads to a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. Further genetic dissection also revealed a redundant and stage-specific role for COM-1 in meiotic HR. Our work thus establishes COM-1/CtIP as a caretaker of germline genome stability and unveils meiotic NHEJ as a potent source of chromosomal aberrations in newborns. JF - PLOS Genetics JA - PLOS Genetics VL - 9 IS - 2 UR - https://doi.org/10.1371/journal.pgen.1003276 SP - e1003276 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1003276 ER -