title: C. elegans germ cells switch between distinct modes of double-strand break repair during meiotic prophase progression.
abstract: Chromosome inheritance during sexual reproduction relies on deliberate induction of double-strand DNA breaks (DSBs) and repair of a subset of these breaks as interhomolog crossovers (COs). Here we provide a direct demonstration, based on our analysis of rad-50 mutants, that the meiotic program in Caenorhabditis elegans involves both acquisition and loss of a specialized mode of double-strand break repair (DSBR). In premeiotic germ cells, RAD-50 is not required to load strand-exchange protein RAD-51 at sites of spontaneous or ionizing radiation (IR)-induced DSBs. A specialized meiotic DSBR mode is engaged at the onset of meiotic prophase, coincident with assembly of meiotic chromosome axis structures. This meiotic DSBR mode is characterized both by dependence on RAD-50 for rapid accumulation of RAD-51 at DSB sites and by competence for converting DSBs into interhomolog COs. At the mid-pachytene to late pachytene transition, germ cells undergo an abrupt release from the meiotic DSBR mode, characterized by reversion to RAD-50-independent loading of RAD-51 and loss of competence to convert DSBs into interhomolog COs. This transition in DSBR mode is dependent on MAP kinase-triggered prophase progression and coincides temporally with a major remodeling of chromosome architecture. We propose that at least two developmentally programmed switches in DSBR mode, likely conferred by changes in chromosome architecture, operate in the C. elegans germ line to allow formation of meiotic crossovers without jeopardizing genomic integrity. Our data further suggest that meiotic cohesin component REC-8 may play a role in limiting the activity of SPO-11 in generating meiotic DSBs and that RAD-50 may function in counteracting this inhibition.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Michiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Chin
authors.forename: Anne M
authors.initials: AM
authors.lastname: Villeneuve
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D023902:Chromosome Pairing / Q000528:radiation effects; D002875:Chromosomes / Q000378:metabolism; D003434:Crossing Over, Genetic / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D049469:Meiotic Prophase I; D009154:Mutation / Q000235:genetics; D049471:Pachytene Stage / Q000528:radiation effects; D051135:Rad51 Recombinase / Q000378:metabolism; D011839:Radiation, Ionizing; D013997:Time Factors; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D029742:Caenorhabditis elegans Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D051135:Rad51 Recombinase; D000099257:Meiotic Recombination Protein SPO11