Transcriptional Activators Stimulate DNA Repair

• Published in: Molecular cell Vol. 10; no. 6; pp. 1391 - 1401
• Main Authors: Frit, Philippe, Kwon, Kyungrim, Coin, Frédéric, Auriol, Jérôme, Dubaele, Sandy, Salles, Bernard, Egly, Jean-Marc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2002; Cell Press
• Subjects: Base Sequence; Binding Sites; Cell Line, Transformed; DNA - chemistry; DNA - metabolism; DNA Repair - physiology; DNA-Binding Proteins; Herpes Simplex Virus Protein Vmw65 - metabolism; Humans; Life Sciences; Oligodeoxyribonucleotides - chemistry; Receptors, Retinoic Acid - metabolism; Recombinant Fusion Proteins - metabolism; Restriction Mapping; Saccharomyces cerevisiae Proteins - metabolism; Simian virus 40 - genetics; Templates, Genetic; Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transfection
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(02)00732-3

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 α-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.