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Condensin-mediated Chromosome Organization and Genome Integrity during Meiosis

$450,000FY2008BIONSF

Florida State University, Tallahassee FL

Investigators

Abstract

The long-term goal of this project is to elucidate the molecular mechanism responsible for the formation of the meiotic chromosome architecture and to examine the role chromosome organization plays in safeguarding genomic integrity. Mitosis and meiosis both require higher-order chromosome organization, which is achieved by the action of a conserved and essential protein complex called condensin. In mitosis, however, there is only one genetic division, that in which paired sister chromatids separate. In contrast, in meiosis two divisions occur. In the first, homologous chromosomes pair, recombine, and then separate; only in the second do the sister chromatids separate. Genetic studies of baker's yeast (Saccharomyces cerevisiae) have confirmed that condensin plays a role in condensation and segregation of meiotic chromosomes. The proposed research is focused on the in vivo cellular and biochemical activities of condensin in meiosis. Three complementary approaches will be employed: (1) A novel three-dimensional chromosome-tracking system will be developed for study of condensin function in chromosome organization and rearrangement at the point of their occurrence in live cells. (2) Genomic and proteomic techniques will be used to identify factors that interact with condensin. Their interaction with condensin will be characterized in the context of DNA topological changes and chromosome segregation. (3) An inducible DNA double-strand break will be created on the chromosome during meiosis so that the role of condensin in repair of the break can be examined. This project involves both undergraduate and graduate students at Florida State University. The feasibility of projects using yeast genetics makes them particularly appropriate and attractive to undergraduate students, including minority students, who participate in a faculty-directed independent study program. This project will therefore enhance the education of undergraduate and graduate students as well as contribute to the advancement of chromosome research.

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