Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
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TTDA与TFIIH的动态相互作用通过活细胞中的核苷酸切除修复稳定。
DOI：
10.1371/journal.pbio.0040156
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发表时间：
2006-06
期刊：
影响因子：
9.8
通讯作者：
Vermeulen W
中科院分区：
文献类型：
--
作者：
Giglia-Mari G;Miquel C;Theil AF;Mari PO;Hoogstraten D;Ng JM;Dinant C;Hoeijmakers JH;Vermeulen W
转录/修复因子IIH(TFIIH)是RNA聚合酶II转录和核苷酸切除修复(NER)所必需的。这个多亚基复合体由10个多肽组成，其中包括最近发现的小8 kDa毛硫代营养不良A组(TTDA)/hTFB5蛋白。属于罕见神经发育修复综合征TTD-A的患者携带TTDA/hTFB5基因的失活突变。这些突变中的一个完全使蛋白质失活，而其他TFIIH基因只容忍不影响转录关键作用的点突变。然而，TTD-A的NER严重缺乏表明TTDA蛋白对修复至关重要。利用TTDA的荧光标记和生物活性版本，我们研究了TTDA在活细胞的修复和转录中的参与。在非挑战性条件下，TTDA存在于两个不同的动力学池中：一个与TFIIH结合，另一个自由部分穿梭于细胞质和细胞核之间。在诱导NER特异性DNA损伤后，这两个池之间的平衡急剧转变为TTDA与TFIIH之间更稳定的关联。调节细胞中的转录活性并没有在这种平衡中引起类似的变化。令人惊讶的是，只引起流产类型的NER反应的DNA构象并不会导致TTDA更稳定地掺入TFIIH。这些发现确认TTDA是体内第一个主要具有NER专职作用的TFIIH亚基，并表明它与TFIIH的相互作用反映了生产性NER。转录/修复因子IIH(TFIIH)是RNA聚合酶II转录和核苷酸切除修复(NER)所必需的多亚基蛋白质复合体。作者发现，TTDA亚基在NER期间与TFIIH有关。
Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER. Transcription/repair factor IIH (TFIIH) is a multi-subunit protein complex essential for RNA polymerase II transcription and nucleotide excision repair (NER). The authors show that the TTDA subunit is associated with TFIIH specifically during NER.
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影响因子：
64.5
作者：
Iben, S;Tschochner, H;Grummt, I
通讯作者：
Grummt, I
活细胞中 RNA 聚合酶 II 的转录周期。
影响因子：
7.8
作者：
Kimura, Hiroshi;Sugaya, Kimihiko;Cook, Peter R
通讯作者：
Cook, Peter R
影响因子：
30.8
作者：
Coin, F;Marinoni, JC;Egly, JM
通讯作者：
Egly, JM
影响因子：
16
作者：
Dubaele, S;De Santis, LP;Egly, JM
通讯作者：
Egly, JM
影响因子：
56.9
作者：
Houtsmuller, AB;Rademakers, S;Vermeulen, W
通讯作者：
Vermeulen, W