title: Brca2-Pds5 complexes mobilize persistent meiotic recombination sites to the nuclear envelope.
abstract: Homologous recombination is required for reciprocal exchange between homologous chromosome arms during meiosis. Only select meiotic recombination events become chromosomal crossovers; the majority of recombination outcomes are noncrossovers. Growing evidence suggests that crossovers are repaired after noncrossovers. Here, I report that persisting recombination sites are mobilized to the nuclear envelope of Drosophila pro-oocytes during mid-pachytene. Their number correlates with the average crossover rate per meiosis. Proteomic and interaction studies reveal that the recombination mediator Brca2 associates with lamin and the cohesion factor Pds5 to secure persistent recombination sites at the nuclear envelope. In Rad51(-/-) females, all persistent DNA breaks are directed to the nuclear envelope. By contrast, a reduction of Pds5 or Brca2 levels abolishes the movement and has a negative impact on crossover rates. The data suggest that persistent meiotic DNA double-strand breaks might correspond to crossovers, which are mobilized to the nuclear envelope for their repair. The identification of Brca2-Pds5 complexes as key mediators of this process provides a first mechanistic explanation for the contribution of lamins and cohesins to meiotic recombination.
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA Thomas.Kusch@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kusch
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics*; D002460:Cell Line; D020090:Chromosome Segregation / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D008540:Meiosis / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics; D009865:Oocytes / Q000166:cytology; D049471:Pachytene Stage / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; C541515:Pds5 protein, Drosophila; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase; C495149:spn-A protein, Drosophila
keywords: Brca2; Cohesin; Homologous recombination; Lamin; Nuclear envelope; Pds5