DUAL ROLE OF TFIIH IN DNA EXCISION-REPAIR AND IN TRANSCRIPTION BY RNA-POLYMERASE-II
DUAL ROLE OF TFIIH IN DNA EXCISION-REPAIR AND IN TRANSCRIPTION BY RNA-POLYMERASE-II
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DOI：
10.1038/368769a0
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发表时间：
1994-04-21
期刊：
影响因子：
64.8
通讯作者：
REINBERG, D
中科院分区：
文献类型：
--
作者：
DRAPKIN, R;REARDON, JT;REINBERG, D
RNA聚合酶II通用转录因子TFIIH由几种多肽组成。TFIIH的最大亚基是切除修复蛋白XPB/ERCC 3（参考文献1），一种与人类DNA修复疾病着色性干皮病（XP）和Cockayne综合征（2，3）有关的解旋酶，这一观察结果表明转录和DNA修复之间存在功能联系（4，5）。为了了解这两个细胞过程之间的联系，我们对TFIIH进行了广泛的纯化和功能分析。我们发现TFIIH具有双重作用，需要II类基因的基础转录和参与DNA切除修复。TFIIH显示出补充切除修复缺陷的三种不同细胞提取物：XPB/ERCC 3、XPC和XPD/ERCC 2。XPB和XPD的互补是ERCC 3和ERCC 2是TFIIH的整合亚基的结果，而XPC的互补是由于该多肽与TFIIH的缔合。我们发现，一般转录因子IIE负调节解旋酶活性的TFIIH通过TFIIE和ERCC 3亚基TFIIH之间的直接相互作用。
THE RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome(2,3), suggests a functional link between transcription and DNA repair(4,5). To understand the connection between these two cellular processes, we have extensively purified and functionally analysed TFIIH. We find that TFIIH has a dual role, being required for basal transcription of class II genes and for participation in DNA-excision repair. TFIIH is shown to complement three different cell extracts deficient in excision repair: XPB/ERCC3, XPC and XPD/ERCC2. The complementation of XPB and XPD is a consequence of ERCC3 and ERCC2 being integral subunits of TFIIH, whereas complementation of XPC is due to an association of this polypeptide with TFIIH. We found that the general transcription factor IIE negatively modulates the helicase activity of TFIIH through a direct interaction between TFIIE and the ERCC3 subunit of TFIIH.