title: Regulation of DNA repair by S-nitrosylation.
abstract: BACKGROUND
  Expression of the inducible nitric oxide synthase (iNOS) is commonly induced in inflammation, an important risk factor of cancer. Nitric oxide (NO) and related reactive nitrogen species can directly cause DNA damage to increase DNA mutation. They can also indirectly affect DNA mutation by modulation of DNA repair proteins, in particular through protein S-nitrosylation, a key regulatory mechanism of NO.
  
  
  METHODS
  Here we review protein targets, molecular mechanisms, and potential roles of NO in the regulation of DNA repair, with a focus on S-nitrosylation of DNA repair proteins by endogenous NO synthase activity.
  
  
  CONCLUSIONS
  Recent studies have identified a number of key DNA repair proteins as targets of S-nitrosylation, including O(6)-alkylguanine-DNA-alkyltransferase (AGT), 8-oxoguanine glycosylase, apurinic-apyrimidinic endonuclease 1, and DNA-dependent protein kinase catalytic subunit. S-nitrosylation has been shown to modulate the activity, stability, and cellular localization of DNA repair proteins. The level of protein S-nitrosylation depends both on NO synthesis by NO synthases and on denitrosylation by a major denitrosylase, S-nitrosoglutathione reductase (GSNOR). Dysregulated S-nitrosylation of AGT due to GSNOR deficiency inactivates AGT-dependent DNA repair and appears to contribute critically to hepatocarcinogenesis.
  
  
  CONCLUSIONS
  Studies on the S-nitrosylation of DNA repair proteins have started to reveal molecular mechanisms for the contribution of inflammation to mutagenesis and carcinogenesis. The modulation of protein S-nitrosylation to affect the activity of DNA repair proteins may provide a therapeutic strategy to prevent DNA damage and mutation frequently associated with chronic inflammation and to sensitize cancer cells to DNA-damaging drugs. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.
authors.affiliation: The Department of Microbiology and Immunology, University of California, San Francisco, CA, United States.
authors.forename: Chi-Hui
authors.initials: CH
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D015538:Nitrosation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D026361:Reactive Nitrogen Species
chemical_list: D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; D019853:O(6)-Methylguanine-DNA Methyltransferase; D019883:Alkyl and Aryl Transferases; C050956:DNA alkyltransferase; D051747:DNA-Activated Protein Kinase; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase