A cut above: Discovery of an alternative excision repair pathway in bacteria

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Abstract
Among the most highly conserved biochemical pathways in free living organisms are those involved in DNA repair (1). The ubiquitous pathway of nucleotide excision repair (NER) is responsible for the removal of environmentally induced DNA damage, such as the DNA lesions resulting from sunlight exposure or chemical carcinogens. Mutations or deficiencies in specific NER genes can lead to premature aging and cancer in humans (2, 3). The study of DNA repair in the bacterium Escherichia coli has helped us to understand the corresponding repair pathways in humans (4). NER can be viewed in four basic steps: ( i ) damage recognition and lesion verification; ( ii ) incision; ( iii ) excision; ( iv ) repair synthesis and ligation, as proposed nearly four decades ago. Damage recognition and verification are achieved by a protein machine that utilizes several components to sense a distortion in the double-helical duplex DNA. In E. coli the UvrA and UvrB proteins carry out these functions. If a putative lesion is identified by UvrA, the repair complex enlists the strand-opening activity of UvrB that helps to verify that the distortion is, in fact, due to a damaged nucleotide. It is believed that the beta-hairpin domain of UvrB is inserted into the DNA helix both to verify the damaged nucleotide and to establish which strand has been damaged (5–9). In both bacterial and eukaryotic species, strand opening and processing of the damage serves to further change the conformation of the DNA to help recruit nucleases to the lesion site to produce two endonucleolytic incisions in the phosphodiester backbone of the damaged strand, one on each side of the altered nucleotide(s). In E. coli , Bacillus caldotenax (9), and presumably in all other free living bacterial species, UvrB recruits the UvrC protein, which contains two functional endonuclease domains. The N-terminal part of this …