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Regulation of Mitotic Centromere-Associated Kinesin

$26,084F31FY2001GMNIH

University Of Washington, Seattle WA

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Abstract

DESCRIPTION (provided by applicant) Mitotic centromere-associate kinesin (MCAK) is one of the principal cytoskeletal proteins involved in cell division. It is localized diffusely in the cytoplasm and nucleus during interphase and is then localized to the centromere from prophase through telophase. MCAK is a microtubule (MT) depolymerizing molecular motor that has been shown to be necessary for proper sister chromatid segregation yet little is known about how it is regulated. Preliminary studies have shown that MCAK constructs lacking the COOH-terminal region have a greater ability to depolymerize Mts when compared to the full-length protein. This proposal intends to investigate the mechanism by which the C-term of MCAK modulates its depolymerization activity. Stable and transient transfections of mutated MCAK DNA will be used to study the potency of the truncated protein. In vivo and in vitro depolymerization assays will be employed to quantify and assess the method of regulation.

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