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.
Frit
Philippe
P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P.163, 67404 Cedex, Illkirch, France.
Kwon
Kyungrim
K
Coin
Frédéric
F
Auriol
Jérôme
J
Dubaele
Sandy
S
Salles
Bernard
B
Egly
Jean Marc
JM
D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013698:Templates, Genetic; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D017405:Herpes Simplex Virus Protein Vmw65; D009838:Oligodeoxyribonucleotides; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA