Role of Set2 in regulating transcription coupled-nucleotide excision repair

Repair of UV damage from the transcribed strand (TS) of yeast genes is rapid due to the transcription coupled nucleotide excision repair (TC-NER) pathway. TC-NER is triggered when RNA polymerase stalls at UV damage, such as a UV-induced cyclobutane pyrimidine dimer (CPD). During transcription, the histone methyltransferase Set2 methylates histone H3K36, but it is not known if Set2 regulates TC-NER. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking Set2. UV-induced CPD lesions were mapped in yeast cells both immediately after UV damage formation (0hr time point) and following two or three hours of repair (2hr or 3hr time point) using the CPD-seq method. Repair of CPD lesions was measured in yeast cells mutated in the gene encoding the Set2 histone methyltransferase or a WT control. Repair was also analyzed in a rad16∆set2∆ double mutant, which is deficient in the global genomic NER (GG-NER) pathway.