Meiotic recombination at the nuclear lamina

Meiotic homologous recombination (HR) produces crossovers, which involve reciprocal exchange of large sections of DNA between homologous chromosomes, and noncrossovers, in which only sequences around the double-strand break (DSB) are exchanged. Evidence from multiple species shows that noncrossover repair occurs before that of crossovers. Here (p. 717), Thomas Kusch investigates HR in Drosophila pro-oocytes. By visualising recombination sites as discrete foci, he found that persistent HR foci moved to the nuclear periphery during pachytene. Mass-spectrometry-based analysis of the factors associated with Brca2, which is required for meiotic HR, revealed that it interacted with the cohesin subunit Pds5, which was enriched at the nuclear periphery. As reported here, Pds5 directly interacts with Brca2 and stabilises its interaction with lamins. Moreover, Pds5 knockdown reduces the DNA-damage-dependent relocalisation of Brca2 to the nuclear envelope. Because Brca2 moves to the nuclear periphery during pachytene, the author hypothesised that Brca2–Pds5 complexes coordinate the anchoring of persistent HR foci at the nuclear envelope. This is indeed the case as pro-oocytes from Brca2 mutants and flies with a germline-specific knockdown of Pds5 both show reduced peripheral localisation of persistent DSBs. In addition, recombination rates are reduced in Pds5^−/+, Brca2^−/+ and Brca2/Pds5 transheterozygotes. Taken together, these results indicate that the nuclear lamina might function as a specific subnuclear compartment for the repair of crossovers.