The Role of XPB/Ssl2 dsDNA Translocase Processivity in Transcription Start-site Scanning.
The Role of XPB/Ssl2 dsDNA Translocase Processivity in Transcription Start-site Scanning.
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DOI：
10.1016/j.jmb.2021.166813
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发表时间：
2021-07-09
影响因子：
5.6
通讯作者：
Galburt EA
中科院分区：
文献类型：
--
作者：
Tomko EJ;Luyties O;Rimel JK;Tsai CL;Fuss JO;Fishburn J;Hahn S;Tsutakawa SE;Taatjes DJ;Galburt EA
一般转录因子TFIIH包含三种ATP依赖的催化活性。TFIIH主要作为DNA解旋酶在核苷酸切除修复中起作用，并且作为dsDNA移位酶和蛋白激酶在Pol II转录起始中起作用。在起始期间，TFIIH的XPB/Ssl 2亚基将ATP水解偶联到dsDNA易位，促进启动子打开，并且激酶模块磷酸化Pol II以促进向延伸的转变。这些功能在后生动物和酵母之间是保守的;然而，酵母TFIIH也驱动转录起始位点扫描，其中Pol II扫描下游DNA以定位生产性起始位点。S.酿酒酵母具有扫描所需的进行性dsDNA移位酶活性，并且在扫描中的结构作用归因于三亚基TFIIH激酶模块。在这里，我们评估了10个亚基的全-和核心-TFIIH复合物（即7个亚基，缺乏激酶模块）的dsDNA移位酶活性。酿酒酵母和H.智人我们发现，无论是全息或核心人类TFIIH表现出进行性易位，在人类缺乏起始位点扫描一致。此外，与holo-TFIIH相反，S.酿酒酵母核心-TFIIH也缺乏进行性易位，其dsDNA刺激的ATP酶活性降低约5倍至与人复合物相当的水平，这可能解释了在不存在S.酿酒酵母激酶模块。这些结果表明，无论是人类还是S。cerevisiae core-TFIIH能有效地转位，而S.酿酒酵母激酶模块充当持续合成因子以允许稳健的转录起始位点扫描。
The general transcription factor TFIIH contains three ATP-dependent catalytic activities. TFIIH functions in nucleotide excision repair primarily as a DNA helicase and in Pol II transcription initiation as a dsDNA translocase and protein kinase. During initiation, the XPB/Ssl2 subunit of TFIIH couples ATP hydrolysis to dsDNA translocation facilitating promoter opening and the kinase module phosphorylates Pol II to facilitate the transition to elongation. These functions are conserved between metazoans and yeast; however, yeast TFIIH also drives transcription start-site scanning in which Pol II scans downstream DNA to locate productive start-sites. The ten-subunit holo-TFIIH from S. cerevisiae has a processive dsDNA translocase activity required for scanning and a structural role in scanning has been ascribed to the three-subunit TFIIH kinase module. Here, we assess the dsDNA translocase activity of ten-subunit holo- and core-TFIIH complexes (i.e. seven subunits, lacking the kinase module) from both S. cerevisiae and H. sapiens. We find that neither holo nor core human TFIIH exhibit processive translocation, consistent with the lack of start-site scanning in humans. Furthermore, in contrast to holo-TFIIH, the S. cerevisiae core-TFIIH also lacks processive translocation and its dsDNA-stimulated ATPase activity was reduced ~5-fold to a level comparable to the human complexes, potentially explaining the reported upstream shift in start-site observed in vitro in the absence of the S. cerevisiae kinase module. These results suggest that neither human nor S. cerevisiae core-TFIIH can translocate efficiently, and that the S. cerevisiae kinase module functions as a processivity factor to allow for robust transcription start-site scanning.
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影响因子：
16
作者：
Luo J;Cimermancic P;Viswanath S;Ebmeier CC;Kim B;Dehecq M;Raman V;Greenberg CH;Pellarin R;Sali A;Taatjes DJ;Hahn S;Ranish J
通讯作者：
Ranish J
影响因子：
16.6
作者：
He, Qing-Li;Titov, Denis V.;Li, Jing;Tan, Minjia;Ye, Zhaohui;Zhao, Yingming;Romo, Daniel;Liu, Jun O.
通讯作者：
Liu, Jun O.
人 TFIIH 激酶 CDK7 调节转录相关的染色质修饰。
影响因子：
8.8
作者：
Ebmeier CC;Erickson B;Allen BL;Allen MA;Kim H;Fong N;Jacobsen JR;Liang K;Shilatifard A;Dowell RD;Old WM;Bentley DL;Taatjes DJ
通讯作者：
Taatjes DJ
影响因子：
12.3
作者：
Qiu, Chenxi;Jin, Huiyan;Kaplan, Craig D.
通讯作者：
Kaplan, Craig D.
DOI：
10.1073/pnas.1417709112
发表时间：
2015-03-31
影响因子：
11.1
作者：
Fishburn, James;Tomko, Eric;Hahn, Steven
通讯作者：
Hahn, Steven