RAD26, THE FUNCTIONAL SACCHAROMYCES-CEREVISIAE HOMOLOG OF THE COCKAYNE-SYNDROME-B GENE ERCC6

Transcription-coupled repair (TCR) is a universal subpathway of the nu cleotide excision repair (NER) system that is limited to the transcrib ed strand of active structural genes. It accomplishes the preferential elimination of transcription-blocking DNA lesions and permits rapid r esumption of the vital process of transcription. A defect in TCR is re sponsible for the rare hereditary disorder Cockayne syndrome (CS). Rec ently we found that mutations in the ERCC6 repair gene, encoding a put ative helicase, underly the repair defect of CS complementation group B. Here we report the cloning and characterization of the Saccharomyce s cerevisiae homolog of CSB/ERCC6, which we designate RAD26. A rad26 d isruption mutant appears viable and grows normally, indicating that th e gene does not have an essential function. In analogy with CS, prefer ential repair of UV-induced cyclobutane pyrimidine dimers in the trans cribed strand of the active RBP2 gene is severely impaired. Surprising ly, in contrast to the human CS mutant, yeast RAD026 disruption does n ot induce any UV-, cisPt- or X-ray sensitivity, explaining why it was not isolated as a mutant before. Recovery of growth after UV exposure was somewhat delayed in rad26. These findings suggest that TCR in lowe r eukaryotes is not very important for cell survival and that the glob al genome repair pathway of NER is the major determinant of cellular r esistance to genotoxicity.