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PXD041679 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTranscription-coupled DNA-Protein Crosslink repair by CSB and CRL4(CSA)-mediated degradation
DescriptionDNA-protein crosslinks (DPCs), arise from enzymatic intermediates, endogenous metabolism or exogenous chemicals like chemotherapeutics. DPCs are highly cytotoxic as they will impede DNA transacting processes such as replication, which is counteracted by proteolysis-mediated DPC removal by the protease SPRTN or the proteasome. However, how DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown. Here, we show that DPCs severely inhibit RNA polymerase II (Pol II)-mediated transcription, resulting in the recruitment of the transcription-coupled nucleotide excision repair (TC-NER) factors CSA and CSB. Interestingly, CSA and CSB are indispensable for transcription-coupled DPC (TC-DPC) repair, while the downstream TC-NER factors UVSSA and XPA are not, indicative of a non-canonical TC-NER mechanism. TC-DPC repair functions independent of SPRTN, but is mediated by the activities of the ubiquitin ligase CRL4CSA and the proteasome. Thus, DPCs are preferentially repaired in genes by a dedicated transcription-coupled repair mechanism, which is crucial to warrant correct transcription.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeroen Demmers
SpeciesList scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitinylated lysine
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-20 04:20:32ID requested
12024-02-09 02:39:21announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: TC-NER, SILAC, CSB, CSA
Contact List
Jeroen Demmers
contact affiliationProteomics center, Erasmus MC
contact emailj.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliationProteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact emailj.demmers@erasmusmc.nl
dataset submitter
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Dataset FTP location
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