Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch Cedex, C.U. Strasbourg, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France; Université de Strasbourg, Illkirch, France.
Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch Cedex, C.U. Strasbourg, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France; Université de Strasbourg, Illkirch, France.
Adv Protein Chem Struct Biol. 2019;115:21-67. doi: 10.1016/bs.apcsb.2019.01.003. Epub 2019 Feb 10.
Transcription factor IIH (TFIIH) is a multiprotein complex involved in both eukaryotic transcription and DNA repair, revealing a tight connection between these two processes. Composed of 10 subunits, it can be resolved into a 7-subunits core complex with the XPB translocase and the XPD helicase, and the 3-subunits kinase complex CAK, which also exists as a free complex with a distinct function. Initially identified as basal transcription factor, TFIIH also participates in transcription regulation and plays a key role in nucleotide excision repair (NER) for opening DNA at damaged sites, lesion verification and recruitment of additional repair factors. Our understanding of TFIIH function in eukaryotic cells has greatly benefited from studies of the genetic rare diseases xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD), that are not only characterized by cancer and aging predispositions but also by neurological and developmental defects. Although much remains unknown about TFIIH function, significant progresses have been done regarding the structure of the complex, the functions of its catalytic subunits and the multiple roles of the regulatory core-TFIIH subunits. This review provides a non-exhaustive survey of key discoveries on the structure and function of this pivotal factor, which can be considered as a promising target for therapeutic strategies.
转录因子 IIH（TFIIH）是一种参与真核转录和 DNA 修复的多蛋白复合物，揭示了这两个过程之间的紧密联系。它由 10 个亚基组成，可以分为一个由 7 个亚基组成的核心复合物，包括 XPB 转位酶和 XPD 解旋酶，以及由 3 个亚基组成的激酶复合物 CAK，CAK 也作为一个具有独特功能的游离复合物存在。TFIIH 最初被鉴定为基础转录因子，它也参与转录调控，并在核苷酸切除修复（NER）中发挥关键作用，以在受损部位打开 DNA、验证损伤并募集其他修复因子。我们对真核细胞中 TFIIH 功能的理解很大程度上受益于对遗传罕见疾病 XP（着色性干皮病）、CS（Cockayne 综合征）和 TTD（毛发硫营养不良症）的研究，这些疾病不仅表现出癌症和衰老倾向，还表现出神经和发育缺陷。尽管 TFIIH 的功能仍有许多未知之处，但在复合物的结构、其催化亚基的功能以及调节核心-TFIIH 亚基的多种作用方面已经取得了重大进展。本文综述了关于这个关键因子的结构和功能的关键发现，TFIIH 可以被视为一种有前途的治疗策略靶标。
