Rad26, the yeast homolog of the cockayne syndrome B gene product, counteracts inhibition of DNA repair due to RNA polymerase II transcription

Transcription-coupled DNA repair (TCR) is responsible for the preferential removal of DNA lesions from the transcribed strands of RNA polymerase II tr anscribed genes. Saccharomyces cerevisiae rad26 mutants and cells from pati ents suffering from the hereditary disease. Cockayne syndrome display a TCR defective phenotype. Whether this lack of preferential repair has to be ex plained by a defect in repair or in general transcription is unclear at pre sent. To discriminate between both possibilities, we analyzed repair of UV- induced cyclobutane pyrimidine dimers at single base resolution in yeast ce lls lacking RAD26, the homolog of the Cockayne syndrome B gene. Disrupting RAD26 affects nucleotide excision repair of transcribed DNA irrespective of the chromatin context, resulting in similar rates of removal for individua l cyclobutane pyrimidine dimers throughout the transcribed strand. Notably, repair of transcribed sequences in between core nucleosomal regions is les s efficient compared with nontranscribed DNA at these positions, pointing t o a nucleotide excision repair impediment caused by blocked RNA polymerase. Our in vivo data demonstrate that the TCR defect in rad26 mutant cells is not due to a general transcription deficiency but results from the inabilit y to release the transcription complex trapped at sites of base damage.