PXD047613

PXD047613 is an original dataset announced via ProteomeXchange.

Title	A site-specific analysis of the ADP-Ribosylome unveils Homogeneous Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines
Description	ADP-ribosylation (ADPr) signaling plays a crucial role in the DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage – PARP1 – are used as targeted therapies against breast cancers with BRCA1/2 mutations. However, development of resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To better understand the role of ADPr in PARPi sensitivity, we used Liquid Chromatography-Mass Spectrometry (LC-MS) for systems level analysis of the ADP-ribosylome in six breast cancer cell lines with different PARPi sensitivities. We identified 1632 sites on 777 proteins, primarily on serine residues, with a high site overlap of DNA damage-related proteins across all cell lines, demonstrating high conservation in ADPr signaling after DNA damage. We furthermore observed site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants, and unique ADPr sites in PARPi-resistant BRCA mutant cells, which we notably show to have low PARG levels and longer PARP1 ADPr chains.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:52:13.173.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Holda Anagho
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	adenosine diphosphoribosyl (ADP-ribosyl) modified residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-07 05:49:46	ID requested
1	2024-08-02 07:52:17	announced
⏵ 2	2024-10-22 06:52:13	announced	2024-10-22: Updated project metadata.

10.1016/J.CELREP.2024.114433;

submitter keyword: proteomics, mass spectrometry, EThcD, PARP inhibitor sensitivity, PARP, Af1521 macrodomain, ADP-ribosylome, PARG,ADP-ribosylation

Michael Lund Nielsen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Holda Anagho
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
contact email	holda.anagho@cpr.ku.dk
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/2024/08/PXD047613

PRIDE project URI

• PRIDE
  1. PXD047613
     1. Label: PRIDE project
     2. Name: A site-specific analysis of the ADP-Ribosylome unveils Homogeneous Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines