Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant

Nucleic Acids Res. 2005 Mar 30;33(6):1813-24. doi: 10.1093/nar/gki325. Print 2005.

Abstract

Numerous lines of evidence support the role of oxidative stress in different types of cancer. A major DNA lesion, 8-oxo-7,8-dihydroguanine (8-oxoG), is formed by reactive oxygen species in the genome under physiological conditions. 8-OxoG is strongly mutagenic, generating G.C-->T.A transversions, a frequent somatic mutation in cancers. hOGG1 was cloned as a gene encoding a DNA glycosylase that specifically recognizes and removes 8-oxoG from 8-oxoG:C base pairs and suppresses G.C-->T.A transversions. In this study, we investigated the subcellular localization and expression of hOGG1 during the cell cycle. Northern blots showed cell-cycle-dependent mRNA expression of the two major hOGG1 isoforms. By using a cell line constitutively expressing hOGG1 fused to enhanced green fluorescence protein (EGFP), we observed a dynamic relocalization of EGFP-hOGG1 to the nucleoli during the S-phase of the cell cycle, and this localization was shown to be linked to transcription. A C/G change that results in an amino acid substitution from serine to cysteine in codon 326 has been reported as a genetic polymorphism and a risk allele for a variety of cancers. We investigated the cellular localization of the corresponding protein, hOGG1-Cys326, fused to EGFP and observed a dramatic effect on its localization that is explained by a change in the phosphorylation status of hOGG1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cell Cycle
  • Cell Nucleolus / enzymology*
  • Chromatin / enzymology
  • Chromosomes, Human / enzymology
  • DNA Glycosylases / analysis
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • Nuclear Matrix / enzymology
  • Phosphorylation
  • Polymorphism, Single Nucleotide*
  • S Phase*
  • Serine / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Serine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human