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Journal of Bacteriology, September 2006, p. 6224-6234, Vol. 188, No. 17
0021-9193/06/$08.00+0     doi:10.1128/JB.00477-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antimutator Role of the DNA Glycosylase mutY Gene in Helicobacter pylori

Shuyan Huang, Josephine Kang, and Martin J. Blaser*

Departments of Microbiology and Medicine, New York University School of Medicine, and VA Medical Center, New York, New York

Received 5 April 2006/ Accepted 8 June 2006

Helicobacter pylori has a highly variable genome with ongoing diversification via inter- and intragenomic recombination and spontaneous mutation. DNA repair genes modulating mutation and recombination rates that influence diversification have not been well characterized for H. pylori. To examine the role of putative base excision repair ung and mutY glycosylase and xthA apurinic/apyrimidinic endonuclease genes in H. pylori, mutants of each were constructed in strain JP26 by allelic exchange. Spontaneous mutation frequencies of JP26 mutY mutants, assessed by rifampin resistance, were consistently higher (26-fold) than that of the wild type, whereas the ung and xthA mutants showed smaller increases. In trans complementation of the JP26 mutY mutant restored spontaneous mutation frequencies to wild-type levels. In cross-species studies, H. pylori mutY complemented an Escherichia coli mutY mutant and vice versa. In contrast, the ung and mutY mutants did not show higher frequencies of intergenomic recombination or greater sensitivity to UV-induced DNA damage than the wild type. The H. pylori mutY open reading frame contains an eight-adenine homonucleotide tract; we provide evidence that this is subject to slipped-strand mispairing, leading to frameshifts that eliminate gene function. Our findings indicate that H. pylori possesses phase-variable base excision repair, consistent with a tension between repair and mutation.


* Corresponding author. Mailing address: Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016. Phone: (212) 263-6394. Fax: (212) 263-3969. E-mail: martin.blaser{at}med.nyu.edu.


Journal of Bacteriology, September 2006, p. 6224-6234, Vol. 188, No. 17
0021-9193/06/$08.00+0     doi:10.1128/JB.00477-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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