Regulation of DNA replication and cellular responses to perturbations in replication in the bacterium Bacillus subtilis

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Goranov, Alexi I

Advisor dc:contributor.advisor

• Alan D. Grossman.

• Biology.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/37261
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/37261

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/37261