title: A new thermosensitive smc-3 allele reveals involvement of cohesin in homologous recombination in C. elegans.
abstract: The cohesin complex is required for the cohesion of sister chromatids and for correct segregation during mitosis and meiosis. Crossover recombination, together with cohesion, is essential for the disjunction of homologous chromosomes during the first meiotic division. Cohesin has been implicated in facilitating recombinational repair of DNA lesions via the sister chromatid. Here, we made use of a new temperature-sensitive mutation in the Caenorhabditis elegans SMC-3 protein to study the role of cohesin in the repair of DNA double-strand breaks (DSBs) and hence in meiotic crossing over. We report that attenuation of cohesin was associated with extensive SPO-11-dependent chromosome fragmentation, which is representative of unrepaired DSBs. We also found that attenuated cohesin likely increased the number of DSBs and eliminated the need of MRE-11 and RAD-50 for DSB formation in C. elegans, which suggests a role for the MRN complex in making cohesin-loaded chromatin susceptible to meiotic DSBs. Notably, in spite of largely intact sister chromatid cohesion, backup DSB repair via the sister chromatid was mostly impaired. We also found that weakened cohesins affected mitotic repair of DSBs by homologous recombination, whereas NHEJ repair was not affected. Our data suggest that recombinational DNA repair makes higher demands on cohesins than does chromosome segregation.
authors.affiliation: Max F. Perutz Laboratories, Department of Chromosome Biology, University of Vienna, Vienna, Austria.
authors.forename: Antoine
authors.initials: A
authors.lastname: Baudrimont
authors.forename: Alexandra
authors.initials: A
authors.lastname: Penkner
authors.forename: Alexander
authors.initials: A
authors.lastname: Woglar
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Mamnun
authors.forename: Margot
authors.initials: M
authors.lastname: Hulek
authors.forename: Cathrin
authors.initials: C
authors.lastname: Struck
authors.forename: Ralf
authors.initials: R
authors.lastname: Schnabel
authors.forename: Josef
authors.initials: J
authors.lastname: Loidl
authors.forename: Verena
authors.initials: V
authors.lastname: Jantsch
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D013696:Temperature; D013737:Testis / Q000254:growth & development; D000097722:Cohesins
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; C569620:SMC-3 protein, C elegans