Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Biology

Supervisor

Dr. Jim Karagiannis

Abstract

A cell cycle checkpoint at the G2/M boundary of fission yeast cells ensures that the G2/M transition of daughter cells only occurs after successful cytokinesis in the mother cell. The Lst complex is necessary for proper functioning of this checkpoint and is orthologous to a human histone de-aceylase complex (HDAC3/NCOR2-SMRT), with a known role in cytokinesis. However, the fission yeast orthologue of the human HDAC3 histone de-acetylase, Hos2p, was never previously characterized with respect to the Lst complex. Through a combination of phenotypic analyses on hos2 mutants, live-cell imaging of Hos2p localization, live-cell imaging of cytokinesis dynamics as they relate to Hos2p’s cytokinetic regulatory function, and co-immunoprecipitation experiments, I showed that Hos2p is indeed a member of the Lst complex, and ensures faithful cytokinesis through its de-acetylase activity. Additionally, I used Western Blotting to show that the Lst complex is a stress-responsive complex that up-regulates expression of its Lstlp sub-unit in response to a sub-set of environmental stressors known to turn on the fission yeast core environmental stress response (CESR). Finally, I show that Hos2p inhibits growth and produces various abnormal phenotypes in a dose-dependent manner, although the biological significance of these observations is unclear.

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