Title
The regulation of translesion synthesis through the binding and activation of polymerases by PCNA
DOI
10.17077/etd.zy8rz6sv
Document Type
Dissertation
Date of Degree
Summer 2016
Degree Name
PhD (Doctor of Philosophy)
Degree In
Biochemistry
First Advisor
Washington, M Todd
First Committee Member
Spies, Maria
Second Committee Member
DeMali, Kris
Third Committee Member
Fuentes, Ernesto
Fourth Committee Member
Shea, Madeline
Fifth Committee Member
Houtman, Jon
Abstract
DNA damage causes replication forks to stall, which can ultimately lead to double strand breaks, chromosomal rearrangements, and cell death. Proliferating cell nuclear antigen is a clamp protein which encircles DNA and acts as a sliding platform for proteins that will act on the DNA, including polymerases. Replication fork stalling causes PCNA to be mono-ubiquitylated, resulting in a polymerase switch from the classical polymerases that perform replication to the Y-family polymerases which conduct translesion synthesis (TLS) to bypass the DNA damage and allow replication to continue. Y-family polymerases include DNA polymerases eta, kappa, iota, and Rev1. The mechanism by which these polymerases are assembled into multi-protein complexes which include PCNA has previously not been well-understood. The studies outlined below demonstrate that ternary complexes involving PCNA, Rev1, and pol η can adopt multiple conformations which can rapidly interconvert. Additionally, I have demonstrated that ubiquitin stimulates the catalytic activity of DNA polymerase eta through a novel interaction with the catalytic core. These studies represent significant progress towards understand the regulation of TLS polymerase activity through both recruitment to and activation by ubiquitylated PCNA.
Pages
ix, 195 pages
Bibliography
Includes bibliographical references (pages 171-195).
Copyright
Copyright © 2016 Elizabeth Marie Boehm
Recommended Citation
Boehm, Elizabeth Marie. "The regulation of translesion synthesis through the binding and activation of polymerases by PCNA." PhD (Doctor of Philosophy) thesis, University of Iowa, 2016.
https://doi.org/10.17077/etd.zy8rz6sv