Exploration of the budding yeast kinase Mck1 in cell cycle regulation
department or school: Medicine, Faculty of
department or school: Medical Genetics, Department of
data provider: DSpace
degree campus: UBCV
creator: McQueen, Jennifer
issued: 2013-08-31T00:00:00
issued: 2012
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: The study of essential cellular processes such as the regulation of the cell cycle and cellular responses to DNA replication stress in model organisms such as the budding yeast Saccharomyces cerevisiae (S. cerevisiae) benefits our understanding of these processes in human cells. The pathways that govern the response to the DNA replication checkpoint as well as those involved in accurate chromosome segregation are vital to prevent genomic instability, which is a cause of cancer. The yeast cell cycle is governed by one cyclindependent kinase, Cdk1, which controls cell cycle transitions by interacting with specific cyclins during G1, S and M phase. Using a combination of genetic and biochemical techniques, I have discovered that Mck1, a homologue of mammalian glycogen synthase kinase 3 (GSK-3), is a novel negative regulator of Cdk1 activity in budding yeast. My thesis also explores a role for Mck1 during the DNA replication checkpoint. Additionally, my work has contributed to the understanding of the mechanisms utilized to restrain spindle elongation during DNA replication stress. My thesis has three main conclusions; 1) The kinase activity of Mck1 is required to inhibit Clb2-Cdk1 activity post-nuclear division. 2) Mck1 kinase activity is required for survival during chronic exposure to DNA replication stress caused by HU in a process other than checkpoint activation. 3) Overexpression of MCK1 rescues the viability of a kinetochore mutant (spc24-9) that is defective in attachment of chromosomes to kinetochore microtubules. In particular, overexpression of Mck1 restrains the precocious spindle elongation that occurs in spc24-9 strains in response to DNA replication stress. Overall, my thesis demonstrates that the Mck1 kinase contributes to regulation of cell cycle progression in budding yeast. This is important as it demonstrates a conserved function with the mammalian homologue, which has been implicated in several diseases including cancer.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/42927
note: EXPLORATION OF THE BUDDING YEAST KINASE MCK1 IN CELL CYCLE REGULATION by Jennifer McQueen B.Sc., The University of British Columbia, 2005 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Genetics) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2012 © Jennifer McQueen, 2012 ii Abstract The study of essential cellular processes such as the regulation of the cell cycle and cellular responses to DNA replication stress in model organisms such as the budding yeast Saccharomyces cerevisiae (S. cerevisiae) benefits our understanding of these processes in human cells. The pathways that govern the response to the DNA replication checkpoint as well as those involved in accurate chromosome segregation are vital to prevent genomic instability, which is a cause of cancer. The yeast cell cycle is governed by one cyclin- dependent kinase, Cdk1, which controls cell cycle transitions by interacting with specific cyclins during G1, S and M phase. Using a combination of genetic and biochemical techniques, I have discovered that Mck1, a homologue of mammalian glycogen synthase kinase 3 (GSK-3), is a novel negative regulator of Cdk1 activity in budding yeast. My thesis also explores a role for Mck1 during the DNA replication checkpoint. Additionally, my work has contributed to the understanding of the mechanisms utilized to restrain spindle elongation during DNA replication stress. My thesis has three main conclusions; 1) The kinase activity of Mck1 is required to inhibit Clb2-Cdk1 activity post-nuclear division. 2) Mck1 kinase activity is required for survival during chronic exposure to DNA replication stress caused by HU in a process other than checkpoint activation. 3) Overexpression of MCK1 rescues the viability of a kinetochore mutant (spc24-9) that is defective in attachment of chromosomes to kinetochore microtubules. In particular, overexpression of Mck1 restrains the precocious spindle …
has type: Thesis/Dissertation
date issued: 2012-11
is shown at: 10.14288/1.0072986
language: eng
degree discipline: Genetics
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 3.0 Unported
rights URI: http://creativecommons.org/licenses/by-nc-nd/3.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/42927