PXD012606

PXD012606 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin ligase WWP2 targets RNA polymerase II in a DNA-PK-dependent transcription shutoff circuitry for DNA repair
Description	DNA double-strand breaks (DSBs) at RNA polymerase II (RNAPII)-transcribed genes lead to inhibition of transcription. DNA protein kinase (DNA-PK) complex plays a pivotal role in transcription inhibition at DSBs by stimulating proteasome-dependent eviction of RNAPII at these lesions. How DNA-PK triggers RNAPII eviction to inhibit transcription at DSBs remained unclear. Here we show that the HECT E3 ubiquitin ligase WWP2 associates with components of the DNA-PK and RNAPII complexes and is recruited to DSBs at RNAPII-transcribed genes. In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII. The lack of WWP2 or expression of non-ubiquitylatable RPB1 abrogates the loading of Non-Homologous End-Joining (NHEJ) factors, including DNA-PK and XRCC4/DNA ligase IV, and impairs DSB repair. These findings suggest that WWP2 operates in a DNA-PK-dependent shut-off circuitry for RNAPII clearance that promotes DSB repair by protecting the NHEJ machinery from collision with the transcription machinery.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:53:04.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alfred Vertegaal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-07 03:43:00	ID requested
1	2019-03-29 01:15:39	announced
⏵ 2	2024-10-22 04:53:04	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biological

submitter keyword: human

Alfred Vertegaal
contact affiliation	Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
contact email	vertegaal@lumc.nl
lab head
Alfred Vertegaal
contact affiliation	Leiden University Medical Center
contact email	vertegaal@lumc.nl
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/2019/03/PXD012606

PRIDE project URI

• PRIDE
  1. PXD012606
     1. Label: PRIDE project
     2. Name: Ubiquitin ligase WWP2 targets RNA polymerase II in a DNA-PK-dependent transcription shutoff circuitry for DNA repair