Chemistry and biology of DNA repair

Numerous agents of endogenous and exogenous origin damage DNA in our genome. There are several DNA-repair pathways that recognize lesions in DNA and remove them through a number of diverse reaction sequences. Defects in DNA-repair proteins are associated with several human hereditary syndromes, which show a marked predisposition to cancer. Although DNA repair is essential for a healthy cell, DNA-repair enzymes counteract the efficiency of a number of important antitumor agents that exert their cytotoxic effects by damaging DNA. DNA-repair enzymes are therefore also targets for drug design. DNA-repair processes differ greatly in their nature and complexity. Whereas some pathways only require a single enzyme to restore the original DNA sequence, others operate through the coordinated action of 30 or more proteins. Our understanding of the genetic, biochemical, and structural basis of DNA repair and related processes has increased dramatically over the past decade. This review summarizes the latest developments in this field.