A conserved function for a Caenorhabditis elegans Com1/Sae2/CtIP protein homolog in meiotic recombination.
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 gamma-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.
Penkner
Alexandra
A
Department of Chromosome Biology and Max F. Perutz Laboratories, Center for Molecular Biology, University of Vienna, Vienna, Austria.
Portik-Dobos
Zsuzsanna
Z
Tang
Lois
L
Schnabel
Ralf
R
Novatchkova
Maria
M
Jantsch
Verena
V
Loidl
Josef
J
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D018509:DNA, Helminth / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases; D005720:Gamma Rays; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D008969:Molecular Sequence Data; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D004277:DNA, Single-Stranded; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; D004720:Endonucleases