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PHYSIOLOGICAL ROLES AND EVOLUTIONARY IMPLICATIONS OF
ALTERNATIVE DNA POLYMERASES IN ESCHERICHIA COLI
by
Christopher Hale Corzett
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR BIOLOGY)
December 2012
Copyright 2012 Christopher Hale Corzett
Object Description
| Title | Physiological roles and evolutionary implications of alternative DNA polymerases in Escherichia coli |
| Author | Corzett, Christopher Hale |
| Author email | corzett@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Biology |
| School | College of Letters, Arts And Sciences |
| Date defended/completed | 2012-05-03 |
| Date submitted | 2012-11-12 |
| Date approved | 2012-11-12 |
| Restricted until | 2012-11-12 |
| Date published | 2012-11-12 |
| Advisor (committee chair) | Finkel, Steven E. |
| Advisor (committee member) |
Goodman, Myron F. Nealson, Kenneth H. Goodman, Steven D. |
| Abstract | Escherichia coli DNA polymerases II, IV and V serve dual roles within cells by facilitating efficient replication past potentially lethal DNA damage while simultaneously introducing genetic variation that can promote adaptation and evolution within stressful environments. While long recognized to be important for these physiological and evolutionary roles, the specific molecular mechanisms and relative contributions attributable to each of these alternative DNA polymerases within natural environmental conditions has remained elusive. Using a series of alternative polymerase-deficient strains analyzed during conditions of both feast and famine, we establish distinct hierarchies of polymerase activity. Pol II confers a significant physiological advantage by facilitating efficient replication and creating genetic diversity during periods of rapid growth, whereas Pol IV and Pol V make the largest contributions to evolutionary fitness during long-term stationary phase. Pol V is responsible for maximizing allelic diversity, yet Pol IV is the single greatest determinant of mutation frequency. Furthermore, we demonstrate that these alternative polymerases, along with additional members of the SOS regulon, are induced as cells transition from exponential to stationary phase growth in the absence of exogenous stress-stimulated SOS induction, and that they remain elevated throughout long-term stationary phase. These findings reveal each alternative DNA polymerase is vital to physiological and evolutionary fitness under dynamic and unpredictable conditions akin to those experienced in nature, and indicate their contributions to replication and adaptation within microbial communities are greater than previously appreciated. |
| Keyword | alternative DNA polymerase; error-prone DNA polymerase; microbial evolution; SOS response; stationary phase; translesion synthesis |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Corzett, Christopher Hale |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-CorzettChr-1285.pdf |
Description
| Title | Page 1 |
| Full text | PHYSIOLOGICAL ROLES AND EVOLUTIONARY IMPLICATIONS OF ALTERNATIVE DNA POLYMERASES IN ESCHERICHIA COLI by Christopher Hale Corzett A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR BIOLOGY) December 2012 Copyright 2012 Christopher Hale Corzett |
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