Published online 30 March 2005
Article |
Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant
1Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, University of Oslo Rikshospitalet, N-0027 Oslo, Norway 2Department of Molecular Biology, Institute of Medical Microbiology, University of Oslo Rikshospitalet, N-0027 Oslo, Norway 3Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology N-7489 Trondheim, Norway 4UPR 9003 du Centre National de la Recherche Scientifique, Universite Louis Pasteur, Ecole Superieure de Biotechnologie de Strasbourg 67412 Illkirch Cedex, France
*To whom correspondence should be addressed. Tel: +47 2307 4069; Fax: +47 2307 4061; Email: luisa.luna{at}labmed.uio.no
Received December 7, 2004. Revised March 8, 2005. Accepted March 8, 2005.
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.
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