Rejuvenation of cohesion during meiotic prophase is required for maintenance of chiasmata and accurate chromosome segregation. Katherine A. Weng, Charlotte A. Jeffreys, Sharon E. Bickel. Biological Sciences, Dartmouth College, Hanover, NH.

   Accurate chromosome segregation in human oocytes requires that meiotic sister chromatid cohesion remain intact for decades and work in model organisms indicates that deterioration of meiotic cohesion over time may be a major determinant of age-related segregation errors. We are using Drosophila to investigate whether oocytes rely exclusively on cohesive linkages that are established during meiotic S phase or if maintenance of meiotic cohesion is an active process that requires rejuvenation throughout the extended period of prophase I. Deco is the Drosophila homolog of the yeast cohesion establishment factor, Eco1, which is required to establish cohesive linkages during S phase. To test the hypothesis that Deco is required for maintenance of meiotic cohesion, we used a Gal4/UAS inducible approach to knock down Deco after meiotic S phase in the female germline. We find that reduction of Deco after meiotic S phase causes premature disassembly of the synaptonemal complex (SC) and increased levels of meiotic nondisjunction (NDJ). Additionally, although chiasmata are formed, they are not maintained. Moreover, SC defects and increased NDJ also occur when cohesin subunits (SMC1, SMC3, SA) and the cohesin loader, Nipped-B are knocked down after meiotic cohesion is established. These data argue that rejuvenation of cohesion requires the loading of new cohesin complexes during meiotic prophase to stabilize chiasmata and ensure proper segregation of meiotic chromosomes. Our data also indicate that Deco-mediated cohesion rejuvenation during prophase I is necessary even in the absence of meiotic double-strand breaks (mei-W68 mutant) and therefore differs from the damage-induced cohesion re-establishment pathway that operates during G2 in yeast vegetative cells. We propose that programmed rejuvenation of cohesive linkages during prophase I represents a critical mechanism that allows metazoan oocytes to counteract the deterioration of cohesion caused by aging. Experiments to investigate the mechanism of cohesion rejuvenation are currently in progress.