title: Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair.
abstract: The nucleotide excision repair machinery can be targeted preferentially to lesions in transcribed sequences. This mode of DNA repair is referred to as transcription-coupled repair (TCR). In yeast, the Rad26 protein, which is the counterpart of the human Cockayne syndrome B protein, is implicated specifically in TCR. In a yeast strain genetically deprived of global genome repair, a deletion of RAD26 renders cells UV sensitive and displays a defect in TCR. Using a genome-wide mutagenesis approach, we found that deletion of the SPT4 gene suppresses the rad26 defect. We show that suppression by the absence of Spt4 is specific for a rad26 defect and is caused by reactivation of TCR in a Rad26-independent manner. Spt4 is involved in the regulation of transcription elongation. The absence of this regulation leads to transcription that is intrinsically competent for TCR. Our findings suggest that Rad26 acts as an elongation factor rendering transcription TCR competent and that its requirement can be modulated by Spt4.
authors: MGC Department of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors: L E
authors: LE
authors: Jansen
authors: H
authors: H
authors: den Dulk
authors: R M
authors: RM
authors: Brouns
authors: M
authors: M
authors: de Ruijter
authors: J A
authors: JA
authors: Brandsma
authors: J
authors: J
authors: Brouwer
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018797:Cell Cycle Proteins; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015723:Gene Library; D005838:Genotype; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008954:Models, Biological; D016296:Mutagenesis; D009687:Nuclear Proteins; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors; D014466:Ultraviolet Rays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; C080991:SPT4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D035602:Transcriptional Elongation Factors; C088086:rad26 protein, S pombe; D008741:Methyl Methanesulfonate