Repairable damage in DNA: overview.

Abstract

Due to the central functional role of DNA and the fact that each cell contains only one or at the most a few copies of each chromosome, damage to DNA has more severe implications for the functional integrity of the cell than does damage to most other cellular components. The chemical makeup and the large target size of chromosomal DNA make it particularly susceptible to attack by exogenous chemical and physical agents. Most, if not all, reactions of exogenous agents with the sugar residues of the DNA backbone result in strand breakage. While the continuity of the sugar-phosphate backbone usually remains intact for reactions involving the heterocyclic bases, such reactions may cause local distortion of the DNA conformation and of the native structure of eukaryotic chromatin. The preservation of the unique three-dimensional structure of the double-stranded DNA helix appears to be a prerequisite for its unimpaired biological activity. DNA base damage and concomitant helix distortion may lead to inhibition of replication and transcription and to a deterioration of the fidelity and a breakdown of the regulation of these processes. Restoration of the structural integrity of the DNA by repair processes is, therefore, a vital function of every cell.