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转录激活因子可刺激DNA修复。

Transcriptional activators stimulate DNA repair.

作者信息

Frit Philippe, Kwon Kyungrim, Coin Frédéric, Auriol Jérôme, Dubaele Sandy, Salles Bernard, Egly Jean Marc

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P.163, 67404 Cedex, Illkirch, France.

出版信息

Mol Cell. 2002 Dec;10(6):1391-401. doi: 10.1016/s1097-2765(02)00732-3.

Abstract

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.

摘要

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。

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