Novel repair activities of AlkA (3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid

Hiroaki Terato, Aya Masaoka, Kenjiro Asagoshi, Akiko Honsho, Yoshihiko Ohyama, Toshinori Suzuki, Masaki Yamada, Keisuke Makino, Kazuo Yamamoto, Hiroshi Ide

Research output: Contribution to journalReview article

45 Citations (Scopus)

Abstract

Nitrosation of guanine in DNA by nitrogen oxides such as nitric oxide (NO) and nitrous acid leads to formation of xanthine (Xan) and oxanine (Oxa), potentially cytotoxic and mutagenic lesions. In the present study, we have examined the repair capacity of DNA N-glycosylases from Escherichia coli for Xan and Oxa. The nicking assay with the defined substrates containing Xan and Oxa revealed that AlkA [in combination with endonuclease (Endo) IV] and Endo VIII recognized Xan in the tested enzymes. The activity (Vmax/Km) of AlkA for Xan was 5-fold lower than that for 7-methylguanine, and that of Endo VIII was 50-fold lower than that for thymine glycol. The activity of AlkA and Endo VIII for Xan was further substantiated by the release of [3H]Xan from the substrate. The treatment of E.coli with N-methyl-N'-nitro-N-nitrosoguanidine increased the Xan-excising activity in the cell extract from alkA+ but not alkA- strains. The alkA and nei (the Endo VIII gene) double mutant, but not the single mutants, exhibited increased sensitivity to nitrous acid relative to the wild type strain. AlkA and Endo VIII also exhibited excision activity for Oxa, but the activity was much lower than that for Xan.

Original languageEnglish
Pages (from-to)4975-4984
Number of pages10
JournalNucleic acids research
Volume30
Issue number22
Publication statusPublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Novel repair activities of AlkA (3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid'. Together they form a unique fingerprint.

  • Cite this

    Terato, H., Masaoka, A., Asagoshi, K., Honsho, A., Ohyama, Y., Suzuki, T., Yamada, M., Makino, K., Yamamoto, K., & Ide, H. (2002). Novel repair activities of AlkA (3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid. Nucleic acids research, 30(22), 4975-4984.