Date of Graduation

12-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biology (PhD)

Degree Level

Graduate

Department

Biological Sciences

Advisor/Mentor

Pinto, Ines

Committee Member

Henry, Ralph L.

Second Committee Member

Lehmann, Michael H.

Third Committee Member

Koeppe, Roger E. II

Keywords

Biological sciences; Chromatin; Chromosome segregation; Deacetylase; Kinetochores

Abstract

Previous work in our lab has identified a point mutation in HTA1, one of the genes encoding histone H2A, which causes an increase-in-ploidy phenotype in Saccharomyces cerevisiae. This histone mutant strain was used to carry out a transposon insertion screen to identify suppressors of the increase-in-ploidy phenotype. This screen identified all three subunits of the Hda histone deacetylase complex, HDA1, HDA2, and HDA3. This study aims to elucidate the function of the Hda complex in chromosome segregation by exploring interactions among the members of the complex, as well as interactions between Hda complex and kinetochore components. We find that the Hda complex interacts with the chromosomal passenger complex (CPC), part of the tension-sensing machinery in the cell. Further experiments on the CPC revealed that a mutant allele of one of the components, BIR1, is synthetically lethal with our original histone H2A mutant. Our results led us to another component of the tension-sensing machinery, SGO1. Interestingly, sgo1 is also synthetically lethal with the histone H2A mutant. Our results indicate that the increase-in-ploidy phenotype of the histone H2A mutant is likely due to the inability to create or sense the adequate tension between kinetochores and microtubules that is necessary for faithful chromosome segregation.

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