Regulation of the mitotic exit network components Tem1 and Cde 15 in Saccharomyces cerevisiae

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2003.
Includes bibliographical references.
The division of a single eukaryotic cell resulting in two daughter progeny is controlled by cyclin dependent kinase activity (CDK). Mitotic cyclins associated with CDK promote the segregation of genetic material ensuring that each daughter receives a complete complement of the genome. In order for exit from mitosis into G1 to occur, mitotic CDK activity must be inactivated. In the budding yeast, Saccharomyces cerevisiae, a network of proteins called the mitotic exit network is essential for mitotic CDK inactivation and, therefore, exit from mitosis. The work presented herein describes the regulation of two components of the mitotic exit network, Teml and Cdc 15. A model for activation of the mitotic exit network is proposed. The spatial separation of the GTPase Teml from its activating GEF, Ltel, until anaphase is suggested to be one signal leading to correct timing of mitotic exit. Additionally, the roles of distinct regions of the protein kinase, CdclS5, are examined. Domains necessary and sufficient for localization of CdclS5 to the spindle pole body, association with other Cdc 15 molecules, and a putative inhibitory domain are investigated. This work investigates the regulatory mechanisms controlling two essential components of the mitotic exit network.
Allison J. Bardin.
Ph.D.