Structural basis of human transcription-DNA repair coupling.
Structural basis of human transcription-DNA repair coupling.
复制标题
DOI：
10.1038/s41586-021-03906-4
复制
发表时间：
2021-10
期刊：
影响因子：
64.8
通讯作者：
Cramer P
中科院分区：
文献类型：
--
作者：
Kokic G;Wagner FR;Chernev A;Urlaub H;Cramer P
转录偶联的DNA修复从基因组中去除大的DNA损伤，并保护细胞免受紫外线（UV）照射。当RNA聚合酶II（Pol II）在DNA损伤处停滞并招募Cockayne综合征蛋白CSB、E3泛素连接酶、CRL 4CSA和UV刺激的支架蛋白A（UVSSA）时，转录偶联DNA修复开始。在这里，我们提供了五个高分辨率的Pol II转录复合物的结构，包含人类转录偶联DNA修复因子和延伸因子PAF 1复合物（PAF）和SPT 6。结合生物化学和已发表的数据，这些结构为转录修复偶联提供了一个模型。Pol II在DNA损伤处的停滞触发CSB替换延伸因子DSIF，CSB结合PAF并将上游DNA移动到SPT 6。由此产生的延伸复合物ECTCR使用CSA刺激的CSB的移位酶活性来拉动上游DNA并将Pol II向前推。如果病变不能绕过，CRL4CSA跨越Pol II钳和泛素化RPB 1残基K1268，使招募TFIIH UVSSA和DNA修复。CRL4CSA的构象变化导致CSB的泛素化，并在转录可能在修复的DNA上继续之前释放转录偶联的DNA修复因子。作者解析了含有RNA聚合酶II和CSA和CSB蛋白的五种复合物的结构，从而深入了解DNA损伤的修复如何与转录偶联。
Transcription-coupled DNA repair removes bulky DNA lesions from the genome and protects cells against ultraviolet (UV) irradiation. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4CSA and UV-stimulated scaffold protein A (UVSSA). Here we provide five high-resolution structures of Pol II transcription complexes containing human transcription-coupled DNA repair factors and the elongation factors PAF1 complex (PAF) and SPT6. Together with biochemical and published data, the structures provide a model for transcription–repair coupling. Stalling of Pol II at a DNA lesion triggers replacement of the elongation factor DSIF by CSB, which binds to PAF and moves upstream DNA to SPT6. The resulting elongation complex, ECTCR, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4CSA spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4CSA lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA. The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.
登录
查看更多内容
影响因子：
4.8
作者：
Citterio, E;Rademakers, S;Vermeulen, W
通讯作者：
Vermeulen, W
影响因子：
16
作者：
Anindya R;Mari PO;Kristensen U;Kool H;Giglia-Mari G;Mullenders LH;Fousteri M;Vermeulen W;Egly JM;Svejstrup JQ
通讯作者：
Svejstrup JQ
影响因子：
56.9
作者：
Brueckner, Florian;Hennecke, Ulrich;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
8.8
作者：
Boeing S;Williamson L;Encheva V;Gori I;Saunders RE;Instrell R;Aygün O;Rodriguez-Martinez M;Weems JC;Kelly GP;Conaway JW;Conaway RC;Stewart A;Howell M;Snijders AP;Svejstrup JQ
通讯作者：
Svejstrup JQ
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH