Antimutator role of the DNA glycosylase mutY gene in Helicobacter pylori.
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.
Huang
Shuyan
S
Department of Microbiology and Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Kang
Josephine
J
Blaser
Martin J
MJ
D000225:Adenine; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D004249:DNA Damage / Q000528:radiation effects; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial / Q000502:physiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000528:radiation effects; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D045647:DNA Glycosylases; D000225:Adenine