9fd2 | pdb_00009fd2
Structure of Pol II-TC-NER-STK19 complex
Structural highlights
FunctionI3LGP4_PIG DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] Publication Abstract from PubMedTranscription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4(CSA) ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4(CSA) serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment. However, the precise regulatory mechanisms of CRL4(CSA) activity and TFIIH recruitment remain elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a TC-NER factor, which is essential for correct DNA damage removal and subsequent transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA, UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability and CRL4(CSA) activity, resulting in efficient RNA Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core TC-NER component. STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.,Ramadhin AR, Lee SH, Zhou D, Salmazo A, Gonzalo-Hansen C, van Sluis M, Blom CMA, Janssens RC, Raams A, Dekkers D, Bezstarosti K, Slade D, Vermeulen W, Pines A, Demmers JAA, Bernecky C, Sixma TK, Marteijn JA Mol Cell. 2024 Nov 13:S1097-2765(24)00870-0. doi: 10.1016/j.molcel.2024.10.030. PMID:39547223[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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