Carcinogenesis Advance Access originally published online on October 31, 2008
Carcinogenesis 2009 30(1):2-10; doi:10.1093/carcin/bgn250
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Published by Oxford University Press 2008.
Base excision repair of oxidative DNA damage and association with cancer and aging
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
1 Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo 05508-000, Brazil
* To whom correspondence should be addressed. Tel: +1 410 558 8162; Fax: +1 410 558 8157; Email: bohrv{at}grc.nia.nih.gov
Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA readily, generating a variety of DNA lesions, such as oxidized bases and strand breaks. If not properly removed, DNA damage can be potentially devastating to normal cell physiology, leading to mutagenesis and/or cell death, especially in the case of cytotoxic lesions that block the progression of DNA/RNA polymerases. Damage-induced mutagenesis has been linked to various malignancies. The major mechanism that cells use to repair oxidative damage lesions, such as 8-hydroxyguanine, formamidopyrimidines, and 5-hydroxyuracil, is base excision repair (BER). The BER pathway in the nucleus is well elucidated. More recently, BER was shown to also exist in the mitochondria. Here, we review the association of BER of oxidative DNA damage with aging, cancer and other diseases.
Abbreviations: ALS, amyotrophic lateral sclerosis; AP, apurinic/apyrimidinic; BER, base excision repair; CI, confidence interval; dRP, 5'-deoxyribose phosphate; DSB, double-strand break; FapyG, 2,6-diamino-4-hydroxy-5-formamidopyrimidine; IR, ionizing radiation; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; NER, nucleotide excision repair; OR, odds ratio; 8-oxoG, 8-hydroxyguanine; POL, polymerase; ROS, reactive oxygen species; SNP, single-nucleotide polymorphism; SSB, single-strand break
Received September 16, 2008; revised October 25, 2008; accepted October 27, 2008.
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