Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant.
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.
Luna
Luisa
L
Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, University of Oslo Rikshospitalet, N-0027 Oslo, Norway. luisa.luna@labmed.uio.no
Rolseth
Veslemøy
V
Hildrestrand
Gunn A
GA
Otterlei
Marit
M
Dantzer
Françoise
F
Bjørås
Magnar
M
Seeberg
Erling
E
D019943:Amino Acid Substitution; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000201:enzymology*; D002843:Chromatin / Q000201:enzymology; D002877:Chromosomes, Human / Q000201:enzymology; D045647:DNA Glycosylases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015530:Nuclear Matrix / Q000201:enzymology; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D016196:S Phase; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012694:Serine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human