Oxidatively induced DNA damage: Mechanisms, repair and disease.

Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. Electronic address: .
Cancer letters (Impact Factor: 4.86). 01/2012; 327(1-2):26-47. DOI: 10.1016/j.canlet.2012.01.016
Source: PubMed

ABSTRACT Endogenous and exogenous sources cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. The resulting DNA lesions are mutagenic and, unless repaired, lead to a variety of mutations and consequently to genetic instability, which is a hallmark of cancer. Oxidatively induced DNA damage is repaired in living cells by different pathways that involve a large number of proteins. Unrepaired and accumulated DNA lesions may lead to disease processes including carcinogenesis. Mutations also occur in DNA repair genes, destabilizing the DNA repair system. A majority of cancer cell lines have somatic mutations in their DNA repair genes. In addition, polymorphisms in these genes constitute a risk factor for cancer. In general, defects in DNA repair are associated with cancer. Numerous DNA repair enzymes exist that possess different, but sometimes overlapping substrate specificities for removal of oxidatively induced DNA lesions. In addition to the role of DNA repair in carcinogenesis, recent evidence suggests that some types of tumors possess increased DNA repair capacity that may lead to therapy resistance. DNA repair pathways are drug targets to develop DNA repair inhibitors to increase the efficacy of cancer therapy. Oxidatively induced DNA lesions and DNA repair proteins may serve as potential biomarkers for early detection, cancer risk assessment, prognosis and for monitoring therapy. Taken together, a large body of accumulated evidence suggests that oxidatively induced DNA damage and its repair are important factors in the development of human cancers. Thus this field deserves more research to contribute to the development of cancer biomarkers, DNA repair inhibitors and treatment approaches to better understand and fight cancer.

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