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

• Published in: The EMBO journal Vol. 26; no. 24; pp. 5071 - 5082
• Main Authors: Penkner, Alexandra, Portik-Dobos, Zsuzsanna, Tang, Lois, Schnabel, Ralf, Novatchkova, Maria, Jantsch, Verena, Loidl, Josef
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 12.12.2007; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Aggregates; Amino Acid Sequence; Animals; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell division; Cellular biology; Chromosomes; crossing over; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA Repair; DNA, Helminth - genetics; DNA, Helminth - metabolism; DNA, Helminth - radiation effects; DNA, Single-Stranded - genetics; DNA, Single-Stranded - metabolism; Endonucleases; Gamma Rays; Genomics; Humans; Mammals; meiosis; Meiosis - physiology; Molecular biology; Molecular Sequence Data; Mutants; Mutation; Proteins; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; recombination; Recombination, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Yeasts
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7601916

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.