Article

DNA damage and repair: from molecular mechanisms to health implications.

Department of Biochemical Sciences, A. Rossi Fanelli, University La Sapienza, Rome, Italy.
Antioxidants and Redox Signaling (impact factor: 8.46). 06/2008; 10(5):891-937. DOI:10.1089/ars.2007.1830 pp.891-937
Source: PubMed

ABSTRACT DNA is subjected to several modifications, resulting from endogenous and exogenous sources. The cell has developed a network of complementary DNA-repair mechanisms, and in the human genome, >130 genes have been found to be involved. Knowledge about the basic mechanisms for DNA repair has revealed an unexpected complexity, with overlapping specificity within the same pathway, as well as extensive functional interactions between proteins involved in repair pathways. Unrepaired or improperly repaired DNA lesions have serious potential consequences for the cell, leading to genomic instability and deregulation of cellular functions. A number of disorders or syndromes, including several cancer predispositions and accelerated aging, are linked to an inherited defect in one of the DNA-repair pathways. Genomic instability, a characteristic of most human malignancies, can also arise from acquired defects in DNA repair, and the specific pathway affected is predictive of types of mutations, tumor drug sensitivity, and treatment outcome. Although DNA repair has received little attention as a determinant of drug sensitivity, emerging knowledge of mutations and polymorphisms in key human DNA-repair genes may provide a rational basis for improved strategies for therapeutic interventions on a number of tumors and degenerative disorders.

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Keywords

basic mechanisms
 
cancer predispositions
 
complementary DNA-repair mechanisms
 
DNA lesions
 
DNA-repair pathways
 
drug sensitivity
 
endogenous
 
extensive functional interactions
 
Genomic instability
 
human genome
 
human malignancies
 
key human DNA-repair genes
 
modifications
 
overlapping specificity
 
rational basis
 
specific pathway
 
therapeutic interventions
 
treatment outcome
 
tumor drug sensitivity
 
unexpected complexity