Publication Date
2019
Document Type
Thesis
Committee Members
Yong-jie Xu, M.D., Ph.D. (Advisor); Michael G. Kemp, Ph.D. (Committee Member); Dawn P. Wooley, Ph.D. (Committee Member); Nancy J. Bigley, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
In response to various perturbations of DNA replication, the DNA replication checkpoint is activated in eukaryotes to stimulate a cascade of cellular responses that are crucial for maintaining genome stability and cell survival. Defects in the checkpoint pathway result in mutations and genome instability, which is a hallmark for cancers. This study used a genetic approach to identify a mutation in the MMS (methyl methanesulfonate) and UV-sensitive protein Mus81, a DNA repair enzyme that resolves aberrant DNA structures through the homologous recombination pathway. We show that a single missense mutation, identified in fission yeast mus81-1, causes moderate reduction in the phosphorylation levels of the major DNA replication checkpoint proteins Mrc1(Claspin) and Cds1(Chk2) in fission yeast. We also show that the mutation directly affects the DNA repair and the DNA damage checkpoint mediated by Chk1 that causes dramatic cell lethality in mus81-1 mutant upon treatment with the DNA damaging agents: MMS, UV and Bleomycin.
Page Count
50
Department or Program
Microbiology and Immunology
Year Degree Awarded
2019
Copyright
Copyright 2019, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
