PXD051638-2

PXD051638 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 DNA 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 stalling of RNA polymerase II at DNA lesions, which triggers the assembly of the TC-NER-specific proteins CSA, CSB and UVSSA. CSA, a WD40-repeat containing protein, is the substrate receptor subunit of a cullin-RING ubiquitin ligase complex composed of DDB1, CUL4A/B and RBX1 (CRL4CSA). Although ubiquitination of several TC-NER proteins by CRL4CSA has been reported, it is still unknown how this complex is regulated. To unravel the dynamic molecular interactions and the regulation of this complex, 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 ubiquitination dynamics during TC-NER and is required for efficient turnover and progression of this process.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:57.309.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Pines
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-22 01:21:55	ID requested
1	2024-05-02 05:49:49	announced
⏵ 2	2024-10-22 06:37:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

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

Alex Pines
contact affiliation	Erasmus MC
contact email	a.pines@erasmusmc.nl
lab head
Alex Pines
contact affiliation	Erasmus MC
contact email	a.pines@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051638
     1. Label: PRIDE project
     2. Name: DDA1, a novel factor in transcription-coupled repair, modulates CRL4CSA dynamics at DNA damage-stalled RNA polymerase II