Transcriptional Activators Stimulate DNA Repair

To counteract the deleterious effects of genotoxic injury, cells have set up a sophisticated network of DNA repair pathways. We show that Gal4-VP16 and RAR transcriptional activators stimulate nucleotide excision repair (NER). This DNA repair activation is not coupled to transcription since it occurs in Cockayne syndrome cells (which are transcription-coupled repair deficient) and is observed in vitro in the presence of alpha-amanitin and in the absence of the basal transcription factors. Using a reconstituted dual incision assay, we also show that binding of activators to their cognate sequences induces a local chromatin remodeling mediated by ATP-driven chromatin remodeling and acetyltransferase activities to facilitate DNA repair.