PXD045415-2

PXD045415 is an original dataset announced via ProteomeXchange.

Title	DDA1, a novel factor in transcription-coupled repair, modulates CRL4CSA dynamics at DNA damage-stalled RNA polymerase II
Description	Transcription–blocking lesions are specifically targeted by transcription-coupled nucleotide excision repair (TC-NER), which removes a broad spectrum of DNA lesions to preserve transcriptional output and thereby cellular homeostasis to counteract aging. TC-NER is initiated by the physical stalling of RNA polymerase II by a DNA damage, which triggers the assembly of TC-NER-specific proteins, including CSA, a WD40 domain containing protein, that forms together with DDB1, CUL4A/B and RBX1, a cullin-RING ubiquitin ligase complex (CRL4CSA). Although ubiquitination of several TC-NER proteins by CSA has been reported, it is still unknown how this complex functions in TC-NER progression. To unravel the molecular mechanism underlying TC-NER, we applied a single-step protein-complex isolation coupled to mass spectrometry analysis and identified DDA1 as a CSA interacting protein. Cryo-EM analysis showed that DDA1 is an integral component of the CRL4CSA complex. Functional analysis revealed that DDA1 coordinates the step-wise ubiquitination during TC-NER and is required for efficient progression of this process by controlling the dynamic turnover of CRL4CSA complex.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:43:28.069.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-15 05:56:56	ID requested
1	2024-05-31 03:48:07	announced
⏵ 2	2024-10-22 06:43:28	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DNA damage-stalled RNA polymerase II, transcription-coupled repair, CRL4CSA dynamics,DDA1

Jeroen Demmers
contact affiliation	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. PXD045415
     1. Label: PRIDE project
     2. Name: DDA1, a novel factor in transcription-coupled repair, modulates CRL4CSA dynamics at DNA damage-stalled RNA polymerase II