Article Text

Download PDFPDF
A variant form of hMTH1, a human homologue of the E coli mutT gene, correlates with somatic mutation in the p53 tumour suppressor gene in gastric cancer patients
  1. Y Kimura1,
  2. S Oda2,
  3. A Egashira1,
  4. Y Kakeji1,
  5. H Baba1,
  6. Y Nakabeppu3,
  7. Y Maehara1
  1. 1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2Department of Pathology, Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan
  3. 3Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, and CREST, JST, Fukuoka, Japan
  1. Correspondence to:
 S Oda
 Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka 811-1395, Japan;

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Oxidative damage to diverse physiological molecules, including proteins, lipids, and nucleic acids, is an inevitable outcome of various cellular activities in living organisms. In particular, some oxidised forms of nucleotides cause miscoding of genetic information, and have therefore been present as a major threat for cells. Multigene systems to counteract such oxidative damage have evolved in diverse organisms. In E coli, several mutants designated ‘mutator’ have been isolated, and in these cells the mutation rate is significantly elevated, due to disruption of genes regulating the spontaneous mutation rate on the genome. Previous studies using these mutators have identified three genes that function in the system to counteract mutagenic oxidative damage. The mutT strain is one of the mutators that exhibit the highest spontaneous mutation rate. Maki H et al have shown that the product of the mutT gene hydrolyses an oxidised form of guanine nucleotides, 8-oxo-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP).1 8-oxo-dGTP incorporated into the genome stably pairs with adenine as well as cytosine in the template strand, accumulation of this oxidised form of guanine nucleotides leads to an increase in base substitution mutations—that is, A:T to G:C and G:C to T:A transversions. In the mutT strain, the rate for A:T to C:G transversion is indeed elevated 1000 fold over the wild type level.2 The other two genes that function in cooperation with mutT are mutM (fpg) and mutY, both of which encode a DNA glycosylase to excise deleterious bases on the genome.3 The former excises 8-oxo-guanine in the opposite site of cytosine on the genome, the latter removing adenine that pairs with 8-oxo-guanine. Thus, even in cells lacking MUT, G:C to T:A transversions are suppressed low.4 Multiplicity of cellular anti-mutagenic systems guarantees the spontaneous mutation rate on the genome at an extremely low …

View Full Text


  • This study was partly supported by a grant from the Ministry of Education, Science, Sports, and Culture of Japan.