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Seminars and Colloquia


Dual roles of Swi6 (Heterochromatin Protein 1) in controlling recombination around centromeres and segregation in meiosis 
Thu, Nov 22, 2018,   11:30 AM to 12:00 PM at Seminar Room 34, 2nd Floor, Main Building

Dr. Mridula Nambiar
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA


In all sexually reproducing species, meiosis generates haploid gametes from diploid cells after two rounds of nuclear division. Meiotic crossovers are essential for error-free chromosome segregation but are specifically repressed near centromeres (pericentric regions) to prevent missegregation. Recognized for >85 years, the molecular mechanism of this repression has remained unknown. To determine the factors that limit pericentric recombination, we study genetically tractable Schizosaccharomyces pombe because, like multicellular eukaryotes, it has large epigenetically maintained centromeres. Meiotic chromosomes contain two distinct cohesin complexes: pericentric complex (for segregation) and chromosomal arm complex (for crossing-over). However, why the cells need to have distinct cohesin complexes during meiosis is not clear. We find that the pericentric-specific complex also actively represses pericentric meiotic double-strand break (DSB) formation and, consequently, crossovers. We uncover the mechanism by which fission yeast heterochromatin protein Swi6 (mammalian HP1-homolog) prevents recruitment of activators of meiotic DSB formation. We further show that localizing the missing activators to wild-type centromeres bypasses repression, generates abundant meiotic crossovers, and reduces gamete viability. We also observe an increased incidence of meiosis I non-disjunction events in such cases. Due to conservation of the proteins involved, the molecular mechanism elucidated here likely extends to other species including humans, where pericentric crossovers can result in disorders such as Down syndrome. These mechanistic insights provide new clues to understand the roles played by multiple cohesin complexes, especially in human infertility, miscarriage and birth defects.