title: Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and for the DNA damage checkpoint.
abstract: BACKGROUND
  Chromosome segregation and the repair of DNA double-strand breaks (DSBs) by homologous recombination require cohesin, the protein complex that mediates sister chromatid cohesion (SCC). In addition, cohesin is also required for the integrity of DNA damage checkpoints in somatic cells, where cohesin loading depends on a conserved complex containing the Scc2/Nipbl protein. Although cohesin is required for the completion of meiotic recombination, little is known about how cohesin promotes the repair of meiotic DSBs and about the factors that promote loading of cohesin during meiosis.
  
  
  RESULTS
  Here we show that during Caenorhabditis elegans meiosis, loading of cohesin requires SCC-2, whereas the cohesin-related complexes condensin and SMC-5/6 can be loaded by mechanisms independent of both SCC-2 and cohesin. Although the lack of cohesin in scc-2 mutants impairs the repair of meiotic DSBs, surprisingly, the persistent DNA damage fails to trigger an apoptotic response of the conserved pachytene DNA damage checkpoint. Mutants carrying an scc-3 allele that abrogates loading of meiotic cohesin are also deficient in the apoptotic response of the pachytene checkpoint, and both scc-2 and scc-3 mutants fail to recruit the DNA damage sensor 9-1-1 complex onto persistent damage sites during meiosis. Furthermore, we show that meiotic cohesin is also required for the timely loading of the RAD-51 recombinase to irradiation-induced DSBs.
  
  
  CONCLUSIONS
  We propose that meiotic cohesin promotes DSB processing and recruitment of DNA damage checkpoint proteins, thus implicating cohesin in the earliest steps of the DNA damage response during meiosis.
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: James
authors.initials: J
authors.lastname: Lightfoot
authors.forename: Sarah
authors.initials: S
authors.lastname: Testori
authors.forename: Consuelo
authors.initials: C
authors.lastname: Barroso
authors.forename: Enrique
authors.initials: E
authors.lastname: Martinez-Perez
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D008540:Meiosis; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D049471:Pachytene Stage; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D000097722:Cohesins; C515656:PQN-85 protein, C elegans; C108312:condensin complexes