This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burgis, N. E. Articles by Cunningham, R. P. Search for Related Content PubMed PubMed Citation Articles by Burgis, N. E. Articles by Cunningham, R. P.

 Previous Article  |  Next Article 

Journal of Bacteriology, May 2003, p. 3101-3110, Vol. 185, No. 10
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.10.3101-3110.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Repair System for Noncanonical Purines in Escherichia coli

Department of Biological Sciences, The University at Albany, State University of New York, Albany, New York 12222

Received 21 November 2002/ Accepted 26 February 2003

Exposure of Escherichia coli strains deficient in molybdopterin biosynthesis (moa) to the purine base N-6-hydroxylaminopurine (HAP) is mutagenic and toxic. We show that moa mutants exposed to HAP also exhibit elevated mutagenesis, a hyperrecombination phenotype, and increased SOS induction. The E. coli rdgB gene encodes a protein homologous to a deoxyribonucleotide triphosphate pyrophosphatase from Methanococcus jannaschii that shows a preference for purine base analogs. moa rdgB mutants are extremely sensitive to killing by HAP and exhibit increased mutagenesis, recombination, and SOS induction upon HAP exposure. Disruption of the endonuclease V gene, nfi, rescues the HAP sensitivity displayed by moa and moa rdgB mutants and reduces the level of recombination and SOS induction, but it increases the level of mutagenesis. Our results suggest that endonuclease V incision of DNA containing HAP leads to increased recombination and SOS induction and even cell death. Double-strand break repair mutants display an increase in HAP sensitivity, which can be reversed by an nfi mutation. This suggests that cell killing may result from an increase in double-strand breaks generated when replication forks encounter endonuclease V-nicked DNA. We propose a pathway for the removal of HAP from purine pools, from deoxynucleotide triphosphate pools, and from DNA, and we suggest a general model for excluding purine base analogs from DNA. The system for HAP removal consists of a molybdoenzyme, thought to detoxify HAP, a deoxyribonucleotide triphosphate pyrophosphatase that removes noncanonical deoxyribonucleotide triphosphates from replication precursor pools, and an endonuclease that initiates the removal of HAP from DNA.

This article has been cited by other articles:

• Burgis, N. E., Cunningham, R. P. (2007). Substrate Specificity of RdgB Protein, a Deoxyribonucleoside Triphosphate Pyrophosphohydrolase. J. Biol. Chem. 282: 3531-3538 [Abstract] [Full Text]  
• Budke, B., Kuzminov, A. (2006). Hypoxanthine Incorporation Is Nonmutagenic in Escherichia coli.. J. Bacteriol. 188: 6553-6560 [Abstract] [Full Text]  
• Erill, I., Jara, M., Salvador, N., Escribano, M., Campoy, S., Barbe, J. (2004). Differences in LexA regulon structure among Proteobacteria through in vivo assisted comparative genomics. Nucleic Acids Res 32: 6617-6626 [Abstract] [Full Text]  
• Hitchcock, T. M., Gao, H., Cao, W. (2004). Cleavage of deoxyoxanosine-containing oligodeoxyribonucleotides by bacterial endonuclease V. Nucleic Acids Res 32: 4071-4080 [Abstract] [Full Text]  
• Poltoratsky, V. P., Wilson, S. H., Kunkel, T. A., Pavlov, Y. I. (2004). Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase. J. Immunol. 172: 4308-4313 [Abstract] [Full Text]