Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2006.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2008
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| Online Access: | http://dspace.mit.edu/handle/1721.1/37261 http://hdl.handle.net/1721.1/37261 |
| _version_ | 1826197288083521536 |
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| author | Goranov, Alexi I |
| author2 | Alan D. Grossman. |
| author_facet | Alan D. Grossman. Goranov, Alexi I |
| author_sort | Goranov, Alexi I |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2006. |
| first_indexed | 2024-09-23T10:45:24Z |
| format | Thesis |
| id | mit-1721.1/37261 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T10:45:24Z |
| publishDate | 2008 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/372612019-04-12T11:53:42Z Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis Regulation of deoxyribonucleic acid replication and cellular responses to perturbations in replication in the bacterium B. subtilis Goranov, Alexi I Alan D. Grossman. Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Dept. of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2006. "September 2006." Includes bibliographical references. When a cell grows and divides to give rise to genetically identical cells, the genome of the cell is duplicated prior to cell-division. The process of genomic duplication is called DNA replication, and is closely coordinated with other processes in the cell, such as growth rate, and cell division. The mechanisms that regulate when DNA replication initiates and how cells respond to perturbations in replication are not well understood. I used the gram-positive bacterium Bacillus subtilis to address these questions. My research showed that a conserved component of the DNA replication machinery, processivity u-clamp, regulates the initiation of replication. This regulation appears to affect the loading of helicase, a replication component that generates the single-strand DNA template for replication. My results indicate that the replication initiation protein DnaA is the likely target of P-clamp regulation. I also observed that in vivo, in B. subtilis, most of the DNA replication machinery, including P-clamp, can associate with the origin of replication before helicase. This is in stark contrast to in vitro studies in other bacteria. I also addressed the question of how B. subtilis responds to perturbations in DNA replication and DNA damage. (cont.) My results demonstrate that the conserved recombination protein, RecA, mediates most of the transcriptional response under the tested conditions. More than 75% of the RecA-mediated transcriptional response is due to the expression of phage and mobile element genes and their indirect effects. Under conditions of replication elongation arrest, there is still a significant recA-independent response, at least part of which is mediated by the replication protein DnaA. The DnaA-mediated response appears to be conserved in other bacteria, as homologues if the affected genes also have DnaA binding sites in their promoter regions. Previously, one of the DnaA regulated genes, sda, has been shown to affect cell viability after perturbations in replication. Here I showed that another DnaA-regulated gene,ftsL, also affects cell survival after replication arrest by coordinating replication and cell-division. I believe that my results have furthered our understanding of how replication is coordinated with other cell-cycle processes, and have raised interesting questions for future investigation. by Alexi I. Goranov. Ph.D. 2008-02-28T16:29:43Z 2008-02-28T16:29:43Z 2006 Thesis http://dspace.mit.edu/handle/1721.1/37261 http://hdl.handle.net/1721.1/37261 85847042 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/37261 http://dspace.mit.edu/handle/1721.1/7582 223 leaves application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Goranov, Alexi I Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title | Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title_full | Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title_fullStr | Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title_full_unstemmed | Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title_short | Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis |
| title_sort | regulation of dna replication and cellular responses to perturbations in replication in the bacterium bacillus subtilis |
| topic | Biology. |
| url | http://dspace.mit.edu/handle/1721.1/37261 http://hdl.handle.net/1721.1/37261 |
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