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The importance of Dfp1 in alkylation damage response and meiosis

Posted on:2012-09-10Degree:Ph.DType:Thesis
University:University of Southern CaliforniaCandidate:Le, Anh-Huy PhanFull Text:PDF
GTID:2452390011954227Subject:Biology
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In Schizosaccharomyces pombe, the DDK complex is a conserved, essential kinase complex consisting of a catalytic subunit, Hsk1 (Cdc7), and its regulatory subunit Dfp1 (Dbf4). Over the years, it has become apparent that the DDK complex has additional roles that go beyond its function in initiation of DNA replication that now include damage checkpoint response and fork stabilization, promotion of centromeric cohesion and chromosome segregation, and induction of prDSBs.;The focus of my research has been to dissect the different roles the DDK complex has outside of DNA replication. Chapter Two describes the role of the DDK complex in maintaining genome stability. We found that the DDK complex has overlapping roles with components of the fork protection complex in stabilizing the fork, but also unique contributions in response to alkylation damage that place it in the translesion synthesis repair pathway.;Chapter Three describes a functional dissection of the importance of the C-terminus in meiosis. I show that the C-terminus of Dfp1 is important for a regulated meiotic program, induction of prDSBs, and proper chromosome segregation by affecting Rec8 cohesin stability.;Chapter Four concludes with a search for new protein-protein interaction partners that suggest a future research path in elucidating further mechanisms the DDK complex may be involved in.
Keywords/Search Tags:DDK complex, Dfp1, Damage, Response
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