Roles and regulation of cohesin cleavage during meiosis. (360G-Wellcome-078241_Z_05_Z)

£2,581,863

The proposed research "Roles and regulation of cohesin during meiosis" aims to elucidate how the process of chromosome segregation is regulated in meiosis. Specifically, the mechanisms that differentially control the destruction of sister chromatid cohesion at centromeres and chromosome arms in meiosis I will be investigated. Budding and fission yeasts will be used to study the mechanism by which centromeric cohesion is protected from separase, while reverse genetics in the mouse will be used to test whether this mechanism also applies to oocytes. Our research will address the following key questions: (1) Are the first and second meiotic divisions in oocytes triggered by cleavage of cohesin's kleisin subunits as in yeast? (2) Is oogenesis really confined to embryos or might it also take place in adults? (3) Does meiotic cohesin have a post-replicative function in the repair of double strand breaks and the formation of crossovers during prophase of meiosis? (4) Do separase and Rec8 cleavage have any function in the process of recombination during meiosis in oocytes? (5) How do shugoshins prevent kleisin cleavage at centromeres during meiosis I in yeast and how are they recruited to centromeres? (6) Is shugoshin also required for protecting centromeric cohesion during meiosis I in oocytes and if so, does it function like its yeast orthologues?In addition to gaining further insight into the secrets of how genomes are inherited, the above research is of central importance for understanding the exact causes of human medical issues such as Down's Syndrome, spontaneous abortion and female infertility, all of which have been linked to chromosome missegregation in meiosis.

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Grant Details

Amount Awarded 2581863
Applicant Surname Nasmyth
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2005-10-17T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Programme Grant
Internal ID 078241/Z/05/Z
Lead Applicant Prof Kim Nasmyth
Partnership Value 2581863
Planned Dates: End Date 2010-12-31T00:00:00+00:00
Planned Dates: Start Date 2006-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East