PXD058988

PXD058988 is an original dataset announced via ProteomeXchange.

Title	K63-Linked Ubiquitylation of S2P-RNAPII Regulates Transcription in a DNA-PK Inter-Dependent Manner in Response to Double-Strand Breaks
Description	DNA double-strand breaks (DSBs) pose a constant challenge to essential biological functions, including transcription, potentially leading to genomic instability. RNA polymerase II (RNAPII) plays a central role in detecting DNA lesions. Due to difficult-to-repair DSBs, RNAPII removal becomes challenging as it relies, among others, on multifaceted ubiquitylation mechanisms that are yet to be delineated. Our data suggests that during DSB repair, the E3 ubiquitin ligase NEDD4 as well as CRL3 complexes, albeit to a lesser extent, engage and catalyze the ubiquitylation of the elongating RNAPII, crafting a specific ubiquitin code for efficient repair. Specifically, NEDD4 is identified as the specific writer of K63-linked ubiquitin chains of S2P-RNAPII under stress as opposed to the total enzyme of RNAPII that is found to be modified mainly with K48 linkages. We find that these ligases, together with the ligase WWP2, exhibit a DNA-PK inter-dependency, driving proficient NHEJ repair and proper resolution of transcription defects caused by DSBs.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:36:05.592.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 06:51:30	ID requested
⏵ 1	2026-05-24 16:36:06	announced

10.1093/nar/gkag347;

submitter keyword: DSBs, ubiquitylation substrates,CUL3, NHEJ., IR, ubiquitin ligase

Tibor Pankotai
contact affiliation	Genome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Szeged, H-6728, Hungary
contact email	pankotai.tibor@szte.hu
lab head
iolanda Vendrell
contact affiliation	Target Discovery Institute, NDMRB
contact email	iolanda.vendrell@ndm.ox.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD058988

PRIDE project URI

• PRIDE
  1. PXD058988
     1. Label: PRIDE project
     2. Name: K63-Linked Ubiquitylation of S2P-RNAPII Regulates Transcription in a DNA-PK Inter-Dependent Manner in Response to Double-Strand Breaks