Frit Philippe, Kwon Kyungrim, Coin Frédéric, Auriol Jérôme, Dubaele Sandy, Salles Bernard, Egly Jean Marc
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P.163, 67404 Cedex, Illkirch, France.
Mol Cell. 2002 Dec;10(6):1391-401. 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 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.
为了对抗基因毒性损伤的有害影响,细胞建立了一个复杂的DNA修复途径网络。我们发现,Gal4-VP16和RAR转录激活因子可刺激核苷酸切除修复(NER)。这种DNA修复激活与转录无关,因为它发生在科凯恩综合征细胞中(这些细胞存在转录偶联修复缺陷),并且在体外α-鹅膏蕈碱存在且基础转录因子缺失的情况下也能观察到。使用重组双切口试验,我们还表明,激活因子与其同源序列的结合会诱导由ATP驱动的染色质重塑和乙酰转移酶活性介导的局部染色质重塑,以促进DNA修复。