PXD018092

PXD018092 is an original dataset announced via ProteomeXchange.

Title	Replication forks proteomics reveals ATM-dependent rewiring of broken forks to promote restart
Description	The fidelity of DNA replication is governed by a network of DNA repair mechanisms. Defects in replication fork protection can fuel genome instability in cancer, while also creating cancer-specific vulnerabilities. Here, we provide a comprehensive proteomic characterization of the replication fork response to topoisomerase 1 inhibition, a widely used mainstay chemotherapy. We reveal profound changes in the fork proteome and chromatin environment in response to seDSBs and topological stress, and classify fork repair factors according to their specificity for broken and stalled forks. These distinct fork responses also oppositely affect nucleosome occupancy and nuclear membrane interactions. ATM inhibition dramatically rewired the fork breakage response, revealing that ATM promotes HR-dependent fork restart by concomitantly promoting DNA-end resection and suppressing DSB associated protein ubiquitination and NHEJ. Together, this collection of damaged fork proteomes provides an ample resource to understand fork repair mechanisms and identify druggable targets and novel cancer vulnerabilities.
HostingRepository	PRIDE
AnnounceDate	2021-01-15
AnnouncementXML	Submission_2021-01-15_05:33:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georg Kustatscher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-18 05:25:58	ID requested
⏵ 1	2021-01-15 05:33:56	announced

Dataset with its publication pending

submitter keyword: DNA replication, SILAC, NCC, nascent chromatin capture

Juri Rappsilber
contact affiliation	Wellcome Centre for Cell Biology University of Edinburgh Michael Swann Building Max Born Crescent Edinburgh EH9 3BF Scotland, UK
contact email	juri.rappsilber@ed.ac.uk
lab head
Georg Kustatscher
contact affiliation	Wellcome Centre for Cell Biology
contact email	georg.kustatscher@ed.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/2021/01/PXD018092

PRIDE project URI

• PRIDE
  1. PXD018092
     1. Label: PRIDE project
     2. Name: Replication forks proteomics reveals ATM-dependent rewiring of broken forks to promote restart