Journal
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
Volume 38, Issue 2-3, Pages 180-190Publisher
WILEY-LISS
DOI: 10.1002/em.1070
Keywords
oxidative DNA damage; reactive oxygen species; base excision repair; replication-associated repair; coordination of repair pathway
Categories
Funding
- NCI NIH HHS [R01 CA053791, R01 CA081063, CA81063, R01 CA084461, CA 84461, CA53791] Funding Source: Medline
- NIEHS NIH HHS [R01 ES008457, ES08457] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA084461, R01CA053791, R01CA081063] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES008457] Funding Source: NIH RePORTER
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Oxidative damage represents the most significant insult to organisms because of continuous production of the reactive oxygen species (ROS) in vivo. Oxidative damage in DNA, a critical target of ROS, is repaired primarily via the base excision repair (BER) pathway which appears to be the simplest among the three excision repair pathways. However, it is now evident that although BER can be carried with four or five enzymes in vitro, a large number of proteins, including some required for nucleotide excision repair (NER), are needed for in vivo repair of oxidative damage. Furthermore, BER in transcribed vs. nontranscribed DNA regions requires distinct sets of proteins, as in the case of NER. We propose an additional complexity in repair of replicating vs. nonreplicating DNA. Unlike DNA bulky adducts, the oxidized base lesions could be incorporated in the nascent DNA strand, repair of which may share components of the mismatch repair process. Distinct enzyme specificities are thus warranted for repair of lesions in the parental vs. nascent DNA strand. Repair synthesis may be carried out by DNA polymerase beta or replicative polymerases delta and epsilon. Thus, multiple subpathways are needed for repairing oxidative DNA damage, and the pathway decision may require coordination of the successive steps in repair. Such coordination includes transfer of the product of a DNA glycosylase to AP-endonuclease, the next enzyme in the pathway. Interactions among proteins in the pathway may also reflect such coordination, characterization of which should help elucidate these subpathways and their in vivo regulation. (C) 2001 Wiley-Liss, Inc.
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