RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6.
Transcription-coupled repair (TCR) is a universal sub-pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes. It accomplishes the preferential elimination of transcription-blocking DNA lesions and permits rapid resumption of the vital process of transcription. A defect in TCR is responsible for the rare hereditary disorder Cockayne syndrome (CS). Recently we found that mutations in the ERCC6 repair gene, encoding a putative helicase, underly the repair defect of CS complementation group B. Here we report the cloning and characterization of the Saccharomyces cerevisiae homolog of CSB/ERCC6, which we designate RAD26. A rad26 disruption mutant appears viable and grows normally, indicating that the gene does not have an essential function. In analogy with CS, preferential repair of UV-induced cyclobutane pyrimidine dimers in the transcribed strand of the active RBP2 gene is severely impaired. Surprisingly, in contrast to the human CS mutant, yeast RAD26 disruption does not 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 lower eukaryotes is not very important for cell survival and that the global genome repair pathway of NER is the major determinant of cellular resistance to genotoxicity.
MGC Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
A J
AJ
van Gool
R
R
Verhage
S M
SM
Swagemakers
P
P
van de Putte
J
J
Brouwer
C
C
Troelstra
D
D
Bootsma
J H
JH
Hoeijmakers
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D003057:Cockayne Syndrome / Q000235:genetics*; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004271:DNA, Fungal / Q000235:genetics* / Q000528:radiation effects; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology*; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D000075223:Poly-ADP-Ribose Binding Proteins; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C088086:rad26 protein, S pombe; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes