PXD047613 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: proteomics, mass spectrometry, EThcD, PARP inhibitor sensitivity, PARP, Af1521 macrodomain, ADP-ribosylome, PARG,ADP-ribosylation |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047613
- Label: PRIDE project
- Name: A site-specific analysis of the ADP-Ribosylome unveils Homogeneous Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines