Proteomics

Dataset Information

0

STK19 drives transcription-coupled nucleotide excision repair by stimulating Pol II ubiquitylation and TFIIH recruitment


ABSTRACT: DNA damage forms a major obstacle for gene transcription by RNA polymerase II (Pol II). Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates transcription-blocking lesions (TBLs), thereby safeguarding accurate transcription, preserving correct cellular function and counteracting aging. TC-NER initiation involves the recognition of lesion-stalled Pol II by CSB, which recruits the CRL4CSA E3 ubiquitin ligase complex and UVSSA. TBL-induced Pol II ubiquitylation at lysine K1268 by CRL4CSA serves as a critical TC-NER checkpoint, governing Pol II stability and initiating TBL excision by TFIIH recruitment. However, the precise regulatory mechanisms of the CRL4CSA E3 ligase activity and TFIIH recruitment remains elusive. Here, we reveal Serine/Threonine Kinase 19 (STK19) as a novel TC-NER factor. Cryo-EM studies revealed that STK19 is an integral part of the Pol II-TC‐NER complex, bridging CSA with UVSSA, RPB1 and downstream DNA. Live-cell imaging and interaction proteomics shows that STK19 stimulates TC-NER complex stability and proper CRL4CSA complex assembly, resulting in Pol II (K1268) ubiquitylation and subsequent UVSSA and TFIIH recruitment. These findings underscore the crucial role of STK19 as a core component of the TC-NER machinery and its key involvement to the cellular responses to genomic injuries that interfere with transcription.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Cockayne Syndrome

SUBMITTER: Jeroen Demmers  

LAB HEAD: Jeroen demmers

PROVIDER: PXD051720 | Pride | 2024-10-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
2304_L_AnishaRamadhin_11MAY_01.raw Raw
2304_L_AnishaRamadhin_11MAY_02.raw Raw
2304_L_AnishaRamadhin_11MAY_03.raw Raw
2304_L_AnishaRamadhin_11MAY_04.raw Raw
2304_L_AnishaRamadhin_11MAY_05.raw Raw
Items per page:
1 - 5 of 99

Similar Datasets

2024-02-09 | PXD041679 | Pride
2021-04-20 | PXD025304 | Pride
2024-05-02 | PXD051638 | Pride
2020-04-18 | GSE148844 | GEO
2022-02-17 | PXD025328 | Pride
2024-05-31 | GSE243603 | GEO
2024-05-31 | PXD045415 | Pride
2023-11-24 | PXD042388 | Pride
2021-07-07 | PXD021211 | Pride
2020-06-30 | GSE145911 | GEO