Startseite Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
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Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids

  • Yusaku Nakabeppu , Kunihiko Sakumi , Katsumi Sakamoto , Daisuke Tsuchimoto , Teruhisa Tsuzuki und Yoshimichi Nakatsu
Veröffentlicht/Copyright: 11. April 2006
Biological Chemistry
Aus der Zeitschrift Band 387 Heft 4

Abstract

Genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are generated both as byproducts of oxygen respiration or molecular executors in the host defense, and by environmental exposure to ionizing radiation and chemicals. To counteract such oxidative damage in nucleic acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2′-deoxyguanosine triphosphate and 2-hydroxy-2′-deoxyadenosine triphosphate (2-OH-dATP), to the corresponding monophosphates. We observed increased susceptibility to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased occurrence of A:T→C:G and G:C→T:A transversion mutations. 8-Oxoguanine (8-oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase, encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of these enzymes leads to increased tumorigenesis in the lung and intestinal tract in mice, respectively. MUTYH deficiency may also increase G:C to T:A transversions through the misincorporation of 2-OH-dATP, especially in the intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in genomic DNA and the repair activity is selectively impaired by a mutation found in patients with autosomal recessive colorectal adenomatous polyposis.

Keywords: 2-hydroxyadenine; 8-oxoguanine; MTH1; MUTYH; OGG1; oxidative damage
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Corresponding author

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Published Online: 2006-04-11
Published in Print: 2006-04-01

©2006 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/BC.2006.050
Schlagwörter für diesen Artikel
2-hydroxyadenine; 8-oxoguanine; MTH1; MUTYH; OGG1; oxidative damage

Artikel in diesem Heft

  1. Highlight: chronic oxidative stress and cancer
  2. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
  3. Does Helicobacter pylori cause gastric cancer via oxidative stress?
  4. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis
  5. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
  6. Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
  7. Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells
  8. Evidence for attenuated cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine removal in cancer patients
  9. The roles of ATP in the dynamics of the actin filaments of the cytoskeleton
  10. Chiral distinction between the enantiomers of bicyclic alcohols by UDP-glucuronosyltransferases 2B7 and 2B17
  11. A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms
  12. Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function
  13. Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue
  14. BID, an interaction partner of protein kinase CK2α
  15. Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity
  16. Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling
  17. Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
  18. A fluorescence assay for rapid detection of ligand binding affinity to HIV-1 gp41
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