Structural basis of TFIIH activation for nucleotide excision repair
Structural basis of TFIIH activation for nucleotide excision repair
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DOI：
10.1038/s41467-019-10745-5
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发表时间：
2019-06-28
影响因子：
16.6
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
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作者：
Kokic, Goran;Chernev, Aleksandar;Cramer, Patrick
核苷酸切除修复（NER）是主要的DNA修复途径，可去除紫外线诱导的大体积DNA损伤。目前还没有在大的多亚基转录因子IIH （TFIIH）周围形成的NER中间体结构。本文报道了含有TFIIH和NER因子XPA的NER中间体的低温电镜结构。与转录构象相比，TFIIH的结构重排使得其atp酶亚基XPB和XPD分别结合双链和单链DNA，这与它们的转位酶和解旋酶活性一致。XPA释放TFIIH的抑制激酶模块，取代XPD中dna结合孔中的“堵塞”元件，并与NER因子一起刺激XPD活性。我们的研究结果解释了TFIIH如何从转录因子转换为修复因子，并为NER通路的机制分析提供了基础。
Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA. Compared to its transcription conformation, the TFIIH structure is rearranged such that its ATPase subunits XPB and XPD bind double-and single-stranded DNA, consistent with their translocase and helicase activities, respectively. XPA releases the inhibitory kinase module of TFIIH, displaces a 'plug' element from the DNA-binding pore in XPD, and together with the NER factor XPG stimulates XPD activity. Our results explain how TFIIH is switched from a transcription to a repair factor, and provide the basis for a mechanistic analysis of the NER pathway.