PXD041679-1

PXD041679 is an original dataset announced via ProteomeXchange.

Title	Transcription-coupled DNA-Protein Crosslink repair by CSB and CRL4(CSA)-mediated degradation
Description	DNA-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.
HostingRepository	PRIDE
AnnounceDate	2024-02-09
AnnouncementXML	Submission_2024-02-09_02:39:21.289.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-20 04:20:32	ID requested
⏵ 1	2024-02-09 02:39:21	announced
2	2024-10-22 06:28:53	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: TC-NER, SILAC, CSB, CSA

Jeroen Demmers
contact affiliation	Proteomics center, Erasmus MC
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041679
     1. Label: PRIDE project
     2. Name: Transcription-coupled DNA-Protein Crosslink repair by CSB and CRL4(CSA)-mediated degradation