当前位置: X-MOL 学术Nat. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II
Nature Communications ( IF 16.6 ) Pub Date : 2022-06-24 , DOI: 10.1038/s41467-022-31329-w
Barbara Steurer 1 , Roel C Janssens 1 , Marit E Geijer 1 , Fernando Aprile-Garcia 2 , Bart Geverts 3 , Arjan F Theil 1 , Barbara Hummel 2 , Martin E van Royen 3 , Bastiaan Evers 4 , René Bernards 4 , Adriaan B Houtsmuller 3 , Ritwick Sawarkar 2, 5 , Jurgen Marteijn 1
Affiliation  

The precise regulation of RNA Polymerase II (Pol II) transcription after genotoxic stress is crucial for proper execution of the DNA damage-induced stress response. While stalling of Pol II on transcription-blocking lesions (TBLs) blocks transcript elongation and initiates DNA repair in cis, TBLs additionally elicit a response in trans that regulates transcription genome-wide. Here we uncover that, after an initial elongation block in cis, TBLs trigger the genome-wide VCP-mediated proteasomal degradation of promoter-bound, P-Ser5-modified Pol II in trans. This degradation is mechanistically distinct from processing of TBL-stalled Pol II, is signaled via GSK3, and contributes to the TBL-induced transcription block, even in transcription-coupled repair-deficient cells. Thus, our data reveal the targeted degradation of promoter-bound Pol II as a critical pathway that allows cells to cope with DNA damage-induced transcription stress and enables the genome-wide adaptation of transcription to genotoxic stress.



中文翻译:

DNA 损伤诱导的转录应激触发启动子结合的 Pol II 的全基因组降解

基因毒性应激后 RNA 聚合酶 II (Pol II) 转录的精确调节对于正确执行 DNA 损伤诱导的应激反应至关重要。虽然 Pol II 在转录阻断病变 (TBLs) 上的停滞会阻止转录物延伸并启动顺式 DNA 修复,但 TBLs 还会引发反式反应,从而调节全基因组范围内的转录。在这里,我们发现,在顺式的初始延伸阻滞后,TBLs 触发了全基因组 VCP 介导的启动子结合的蛋白酶体降解,P-Ser5 修饰的 Pol II 反式。这种降解在机制上与 TBL 停滞​​的 Pol II 的处理不同,通过 GSK3 发出信号,并有助于 TBL 诱导的转录阻断,即使在转录偶联修复缺陷细胞中也是如此。因此,

更新日期:2022-06-24
down
wechat
bug