A conserved function for a Caenorhabditis elegans Com1/Sae2/CtIP protein homolog in meiotic recombination

Abstract

Genome stability relies on faithful DNA repair both in mitosis and in meiosis. Here, we report on a Caenorhabditis elegans protein that we found to be homologous to the mammalian repair‐related protein CtIP and to the budding yeast Com1/Sae2 recombination protein. A com‐1 mutant displays normal meiotic chromosome pairing but forms irregular chromatin aggregates instead of diakinesis bivalents. While meiotic DNA double‐strand breaks (DSBs) are formed, they appear to persist or undergo improper repair. Despite the presence of DSBs, the recombination protein RAD‐51, which is known to associate with single‐stranded DNA (ssDNA) flanking DSBs, does not localize to meiotic chromosomes in the com‐1 mutant. Exposure of the mutant to γ‐radiation, however, induces RAD‐51 foci, which suggests that the failure of RAD‐51 to load is specific to meiotic (SPO‐11‐generated) DSBs. These results suggest that C. elegans COM‐1 plays a role in the generation of ssDNA tails that can load RAD‐51, invade homologous DNA tracts and thereby initiate recombination. Extrapolating from the worm homolog, we expect similar phenotypes for mutations in the mammalian tumor suppressor CtIP.