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Permanent link (DOI): https://doi.org/10.7939/R3RW8P

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Epigenetic Regulation of Centromere Formation and Kinetochore Function Open Access

Descriptions

Other title
Subject/Keyword
centromere
methylation
mitosis
histones
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Heit, Ryan
Supervisor and department
Hendzel, Michael (Oncology)
Examining committee member and department
Campbell, Robert (Chemistry)
Chan, Gordon (Oncology)
Underhill, Alan (Oncology)
Department
Department of Oncology
Specialization

Date accepted
2009-08-27T15:26:50Z
Graduation date
2009-11
Degree
Master of Science
Degree level
Master's
Abstract
One form of protein regulation is accomplished by post-translational modification (PTM). In order to test the importance one type of PTM, methylation, in chromosome segregation, we inhibited protein methylation for brief periods in G2 using the general methylation inhibitor adenosine dialdehyde (AdOx). Inhibiting methylation solely in late G2 leads to mitotic defects. We observed that several methylated histone residues; H3K9me3, H4K20me3 and H4K20me1, are predominantly affected by AdOx in G2. We show both that the kinetochore proteins are not affected and that the mitotic checkpoint is intact. Further, we observed structural defects and chromosome misalignment in mitotic cells. These results indicate that methylation events during late G2 operate to maintain and ensure the structural integrity of pericentromeric heterochromatin prior to mitosis. These results suggest that pericentromeric heterochromatin is required for the proper sensing of kinetochore tension and inactivation of the mitotic checkpoint.
Language
English
DOI
doi:10.7939/R3RW8P
Rights
License granted by Ryan Heit (rheit@ualberta.ca) on 2009-08-26T22:24:10Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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