Upon DNA damage, eukaryotic cells activate a conserved signal transduction cascade known as the DNA damage checkpoint (DDC). We investigated the influence of DDC kinases on nucleotide excision repair in Saccharomyces cerevisiae and found that repair of both strands of an active gene is affected by Mec1, but not by the downstream checkpoint kinases, Rad53 and Chk1. Repair of the non-transcribed strand (by global genome repair) requires new protein synthesis, possibly reflecting the involvement of Mec1 in the activation of repair genes. In contrast, repair of the transcribed strand by transcription-coupled NER (TC-NER) occurs in the absence of new protein synthesis, and DNA damage results in Mec1-dependent, but Rad53-, Chk1-, Tel1, and Dun1-independent, phosphorylation of the TC-NER factor Rad26, a member of the Swi/Snf group of ATP-dependent translocases and yeast homologue of Cockayne Syndrome B. Mutation of the Rad26 phosphorylation site results in a decrease in the rate of TC-NER, pointing to direct activation of Rad26 by Mec1 kinase. These findings establish a direct role for Mec1 kinase in transcription-coupled repair, at least partly via phosphorylation of Rad26, the main transcription-repair coupling factor.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|