Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair

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 spe cifically in TCR. In a yeast strain genetically deprived of global genome r epair, a deletion of RAD26 renders cells UV sensitive and displays a defect in TCR. Using a genome-wide mutagenesis approach, we found that deletion o f the SPT4 gene suppresses the rad26 defect. We show that suppression by th e absence of Spt4 is specific for a rad26 defect and is caused by reactivat ion of TCR in a Rad26-independent manner. Spt4 is involved in the regulatio n of transcription elongation. The absence of this regulation leads to tran scription that is intrinsically competent for TCR. Our findings suggest tha t Rad26 acts as an elongation factor rendering transcription TCR competent and that its requirement can be modulated by Spt4.