Date of Graduation

12-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Pinto, Ines

Committee Member

Erf, Gisela F.

Second Committee Member

Henry, Ralph L.

Third Committee Member

Lehmann, Michael H.

Keywords

Biological sciences; Centromeres; Chromatin; Chromosome segregation; Histones

Abstract

Histone H2A plays an important role in chromosomal segregation among parent and daughter cells during mitosis. While it is established that this histone is important in maintaining chromosome number in cell, further work is carried out to explore the role of other histones like H3 and H4 for similar effects. A systematic study is initiated by screening a library based on mutation of different amino acid residues in these histones. This detailed screening identified specific regions within H3 and H4, which are critically important for centromeric function. These histones residing near the DNA entry/exit region of nucleosome effects the functionality of cell cycle protein, Sgo1, which in turn helps maintaining error free cell cycle by sensing proper tension among sister chromatids during anaphase of mitosis. This work shows that a mutation in H3 and H4 at the DNA entry/exit region moderately effects the nucleosome structure and reduces the centromeric and pericentromeric localization of Sgo1.

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