Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide

M. Jaiswal, Nicholas F La Russo, N. Nishioka, Y. Nakabeppu, Gregory James Gores

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

NO-mediated inhibition of base excision DNA repair may potentiate oxidative DNA damage in cells and could be relevant to carcinogenesis associated with chronic inflammation. Because 8-oxoguanine, a ubiquitous oxidative DNA lesion, is repaired predominantly by human 8-oxoguanine glycosylase (hOgg1), our aim was to determine whether NO directly inhibits its repair activity. Neither induction of NO-generating enzyme inducible NO synthase nor treatment with S-nitroso-N-acetyl-D-L-pencillamine altered expression of hOgg1 in a human cholangiocarcinoma cell line (KMBC). In contrast, both treatments completely inhibited activity of hOgg1 immunoprecipitated from KMBC cells overexpressing hOgg1 and in a cell-free system. Both NO and peroxynitrite were capable of inhibiting hOgg1 activity. Inhibition of hOgg1 protein was characterized by formation of S-nitrosothiol adducts and loss/ejection of zinc ions. Our data indicate that NO, an inflammatory mediator, directly inhibits a key base excision repair enzyme (hOgg1) responsible for base excision repair of 8-oxoguanine. These data support the concept that NO-mediated inhibition of DNA contributes to the mutagenic environment of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)6388-6393
Number of pages6
JournalCancer Research
Volume61
Issue number17
StatePublished - Aug 1 2001

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DNA Repair
Nitric Oxide
Proteins
S-Nitrosothiols
Inflammation
Peroxynitrous Acid
Cholangiocarcinoma
Cell-Free System
DNA
Enzymes
Nitric Oxide Synthase
DNA Damage
Zinc
Carcinogenesis
Ions
Cell Line
8-hydroxyguanine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide. / Jaiswal, M.; La Russo, Nicholas F; Nishioka, N.; Nakabeppu, Y.; Gores, Gregory James.

In: Cancer Research, Vol. 61, No. 17, 01.08.2001, p. 6388-6393.

Research output: Contribution to journalArticle

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