PXD037677

PXD037677 is an original dataset announced via ProteomeXchange.

Title	HUWE1 interaction partners in HCT116 cells (TMT)
Description	Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:52.026.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Elias Einig
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-24 01:59:49	ID requested
1	2023-07-31 05:19:35	announced
2	2023-08-25 22:34:09	announced	2023-08-26: Updated project metadata.
⏵ 3	2023-11-14 09:05:00	announced	2023-11-14: Updated project metadata.

Einig E, Jin C, Andrioletti V, Macek B, Popov N, RNAPII-dependent ATM signaling at collisions with replication forks. Nat Commun, 14(1):5147(2023) [pubmed]

submitter keyword: Human, WRNIP1, HCT116, HUWE1

Nikita Popov
contact affiliation	Medical Oncology and Pulmonology, University Hospital Tübingen, Germany
contact email	nbpopov@gmail.com
lab head
Elias Einig
contact affiliation	Medical Oncology and Pulmonology, University Hospital Tübingen, Germany
contact email	einig.elias@gmail.com
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/2023/07/PXD037677

PRIDE project URI

• PRIDE
  1. PXD037677
     1. Label: PRIDE project
     2. Name: HUWE1 interaction partners in HCT116 cells (TMT)