A novel role for the transcriptional modulator NusA in DNA repair/damage tolerance pathways in Escherichia coli

All organisms must contend with the consequences of DNA damage, induced by a variety of both endogenous and exogenous sources. Mechanisms of DNA repair and DNA damage tolerance are crucial for cellular survival after DNA damage. Translesion DNA synthesis (TLS) is one such mechanism of DNA damage tolerance which utilizes a specialized translesion DNA polymerase capable of catalyzing DNA synthesis on imperfect templates. There are two TLS polymerases present in Escherichia coli encoded by the dinB (Pol IV) and umuDC (Pol V) gene products. While TLS polymerases provide a variety of benefits to the cell, it is important that they are properly regulated as they have reduced fidelity on undamaged DNA compared to replicative DNA polymerases. Here I present evidence that the essential transcriptional modulator NusA associates with TLS polymerases in E. coli both physically, as noted for DinB, and genetically, with DinB and the umuDC gene products. Mutation of nusA renders cells sensitive to DNA damaging agents and produces phenotypes reminiscent of mutants with altered DNA processing. Moreover, I report that the nusAll mutation completely eliminates the formation of adaptive mutants, revealing that nusA+ function is required for cells to adapt and mutate in response to stress. Though the phenomenon of adaptive mutagenesis also requires dinB+, my data suggest that the role for nusA in adaptive mutagenesis extends beyond an interaction with DinB.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Cohen, Susan E., Ph. D. Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• Graham C. Walker.

• 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/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/47877

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/47877