Base Excision Repair of Oxidative DNA Damage and Association with Cancer and Aging

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2008 Nov 4

PMID 18978338

Citations 257

Authors

Scott Maynard

Shepherd H Schurman

Charlotte Harboe

Nadja C de Souza-Pinto

Vilhelm A Bohr

Affiliations

Soon will be listed here.

Abstract

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.

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