Abstract
Oxygen radicals are produced in all cells either by the normal cellular metabolism or by the exposure to external mutagens. The reactive oxygen species (ROS) generated can induce DNA damage. Among the principal lesions found in DNA due to ROS is an oxidized form of guanine, 8-oxo-7,8-dihydroguanine (8-oxoG). The biological relevance of this lesion has been unveiled by the study of Escherichia colt and Saccharomyces cerevisiae genes involved in the neutralization of the mutagenic effects of 8-oxoG (Cabrera et al., 1988; Nghiem et al., 1988; Radicella et al., 1988; van der Kemp et al., 1996). These genes fpg and mutY for E. colt and OGG1 for yeast, code for DNA glycosylases. Inactivation of any of those genes leads to a spontaneous mutator phenotype characterized by the exclusive increase of GC->TA transversions. In yeast, the OGG1 gene encodes a DNA glycosylase/AP lyase that excises 8-oxoG from DNA. A similar activity has been established in mammals by the recent cloning of the human and rodent OGG1 (reviewed in Boiteux and Radicella (2000)). Consistent with the yeast findings, knock-out mice for OGG1 accumulate abnormal levels of 8-oxoG in their genome and show a moderately elevated spontaneous mutation rate in non proliferative tissues (Klungland et al., 1999). In human cells, the OGG1 gene is located on chromosome 3p25 and encodes two forms of hOggl protein resulting from an alternative splicing of a single RNA. The α-hOggl protein has a nuclear localization whereas the β-hOgg1 is targeted to the mitochondrion (Nishioka et al., 1999).
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References
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Dhénaut, A., Hollenbach, S., Eckert, I., Epe, B., Boiteux, S., Radicella, J.P. (2001). Characterization of hOGG1 Promoter Structure, Expression During Cell Cycle and Overexpression in Mammalian Cells. In: Dansette, P.M., et al. Biological Reactive Intermediates VI. Advances in Experimental Medicine and Biology, vol 500. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0667-6_90
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DOI: https://doi.org/10.1007/978-1-4615-0667-6_90
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