Base excision repair of oxidative DNA damage and association with cancer and aging

TY - JOUR

T1 - Base excision repair of oxidative DNA damage and association with cancer and aging

AU - Maynard, Scott

AU - Schurman, Shepherd H

AU - Harboe, Charlotte

AU - de Souza-Pinto, Nadja C

AU - Bohr, Vilhelm A

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - Aging

KW - Animals

KW - Base Pairing

KW - DNA Damage

KW - DNA Repair

KW - Humans

KW - Neoplasms

KW - Oxidative Stress

KW - Reactive Oxygen Species

KW - Subcellular Fractions

U2 - 10.1093/carcin/bgn250

DO - 10.1093/carcin/bgn250

M3 - Journal article

C2 - 18978338

SN - 0143-3334

VL - 30

SP - 2

EP - 10

JO - Carcinogenesis

JF - Carcinogenesis

IS - 1

ER -