Molecular basis of DNA repair mechanisms and syndromes.

Abstract

Numerous chemical agents and various types of radiation (e.g. UV-light, X-rays) induce a wide range of lesions in DNA. Such damage can lead to changes in the nucleotide sequence varying from point mutations to gross chromosomal aberrations which can alter the expression or functioning of genes implicated in regulation of cell proliferation and differentiation, thereby forwarding the cell in the multistep process of carcinogenesis. To prevent these and other deleterious consequences of DNA injury, all living organisms are equipped with a complex network of DNA repair systems. One of the best studied repair processes is the nucleotide excision repair (NER) pathway which removes a wide diversity of DNA lesions including cyclobutane pyrimidine dimers and (6–4) photoproducts as well as chemical adducts and cross-links. In most — if not all — organisms two NER subpathways operate. One deals with the rapid and efficient removal of lesions that block transcription and thus need to be eliminated urgently (transcription-coupled repair, TCR). The other accomplishes the slower and less efficient global genome repair (GGR) of bulk DNA, including the nontranscribed strand of active genes.