title: Endonuclease V protects Escherichia coli against specific mutations caused by nitrous acid.
abstract: Endonuclease V (deoxyinosine 3'-endonuclease) of Escherichia coli K-12 is a putative DNA repair enzyme that cleaves DNA's containing hypoxanthine, uracil, or mismatched bases. An endonuclease V (nfi) mutation was tested for specific mutator effects on a battery of trp and lac mutant alleles. No marked differences were seen in frequencies of spontaneous reversion. However, when nfi mutants were treated with nitrous acid at a level that was not noticeably mutagenic for nfi(+) strains, they displayed a high frequency of A:T-->G:C, and G:C-->A:T transition mutations. Nitrous acid can deaminate guanine in DNA to xanthine, cytosine to uracil, and adenine to hypoxanthine. The nitrous acid-induced A:T-->G:C transitions were consistent with a role for endonuclease V in the repair of deaminated adenine residues. A confirmatory finding was that the mutagenesis was depressed at a locus containing N(6)-methyladenine, which is known to be relatively resistant to nitrosative deamination. An alkA mutation did not significantly enhance the frequency of A:T-->G:C mutations in an nfi mutant, even though AlkA (3-methyladenine-DNA glycosylase II) has hypoxanthine-DNA glycosylase activity. The nfi mutants also displayed high frequencies of nitrous acid-induced G:C-->A:T transitions. These mutations could not be explained by cytosine deamination because an ung (uracil-DNA N-glycosylase) mutant was not similarly affected. However, these findings are consistent with a role for endonuclease V in the removal of deaminated guanine, i.e., xanthine, from DNA. The results suggest that endonuclease V helps to protect the cell against the mutagenic effects of nitrosative deamination.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Schouten
authors.forename: B
authors.initials: B
authors.lastname: Weiss
mesh_terms: D045647:DNA Glycosylases; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D009608:Nitrous Acid / Q000494:pharmacology*; D014364:Tryptophan / Q000235:genetics; D051981:Uracil-DNA Glycosidase
chemical_list: D009153:Mutagens; D014364:Tryptophan; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C076131:DNA-3-methyladenine glycosidase II; D009608:Nitrous Acid