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Journal of Bacteriology, August 2009, p. 4959-4965, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00495-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nucleotide Excision Repair Is a Predominant Mechanism for Processing Nitrofurazone-Induced DNA Damage in Escherichia coli{triangledown}

Katherine R. Ona,* Charmain T. Courcelle, and Justin Courcelle

Department of Biology, Portland State University, Portland, Oregon 97207

Received 9 April 2009/ Accepted 18 May 2009

Nitrofurazone is reduced by cellular nitroreductases to form N2-deoxyguanine (N2-dG) adducts that are associated with mutagenesis and lethality. Much attention recently has been given to the role that the highly conserved polymerase IV (Pol IV) family of polymerases plays in tolerating adducts induced by nitrofurazone and other N2-dG-generating agents, yet little is known about how nitrofurazone-induced DNA damage is processed by the cell. In this study, we characterized the genetic repair pathways that contribute to survival and mutagenesis in Escherichia coli cultures grown in the presence of nitrofurazone. We find that nucleotide excision repair is a primary mechanism for processing damage induced by nitrofurazone. The contribution of translesion synthesis to survival was minor compared to that of nucleotide excision repair and depended upon Pol IV. In addition, survival also depended on both the RecF and RecBCD pathways. We also found that nitrofurazone acts as a direct inhibitor of DNA replication at higher concentrations. We show that the direct inhibition of replication by nitrofurazone occurs independently of DNA damage and is reversible once the nitrofurazone is removed. Previous studies that reported nucleotide excision repair mutants that were fully resistant to nitrofurazone used high concentrations of the drug (200 µM) and short exposure times. We demonstrate here that these conditions inhibit replication but are insufficient in duration to induce significant levels of DNA damage.

* Corresponding author. Mailing address: Department of Biology, Portland State University, P.O. Box 751, Portland, OR 97201. Phone and fax: (503) 725-3865. E-mail: kro{at}pdx.edu

{triangledown} Published ahead of print on 22 May 2009.

Journal of Bacteriology, August 2009, p. 4959-4965, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00495-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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