Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase separation to inhibit global transcription after DNA damage
| العنوان: | Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase separation to inhibit global transcription after DNA damage |
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| المؤلفون: | Huanyi Fu, Rongdiao Liu, Zixuan Jia, Ran Li, Feifeng Zhu, Wenxuan Zhu, Yangqing Shao, Yiyang Jin, Yuhua Xue, Jun Huang, Kunxin Luo, Xiang Gao, Huasong Lu, Qiang Zhou |
| المصدر: | Nature cell biology, vol 24, iss 4 Nat Cell Biol |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cyclin T, Prevention, 1.1 Normal biological development and functioning, Cell Biology, Biological Sciences, Medical and Health Sciences, Article, ADP-Ribosylation, Underpinning research, Genetics, Positive Transcriptional Elongation Factor B, RNA Polymerase II, Generic health relevance, DNA Damage, Developmental Biology |
| الوصف: | DNA damage shuts down genome-wide transcription to prevent transcriptional mutagenesis and to initiate repair signalling, but the mechanism to stall elongating RNA polymerase II (Pol II) is not fully understood. Central to the DNA damage response, poly(ADP-ribose) polymerase 1 (PARP1) initiates DNA repair by translocating to the lesions where it catalyses protein poly(ADP-ribosylation). Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. This prevents CycT1 from undergoing liquid-liquid phase separation that is required for CDK9 to hyperphosphorylate Pol II and to stimulate elongation. Functionally, poly(ADP-ribosylation) of CycT1 promotes DNA repair and cell survival. Thus, the P-TEFb-PARP1 signalling plays a protective role in transcription quality control and genomic stability maintenance after DNA damage. |
| وصف الملف: | application/pdf |
| تدمد: | 1476-4679 1465-7392 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::350f7dc1919e454ac919f9e56ff3c5f8 https://doi.org/10.1038/s41556-022-00872-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....350f7dc1919e454ac919f9e56ff3c5f8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764679 14657392 |
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