PXD066208

PXD066208 is an original dataset announced via ProteomeXchange.

Title	A Versatile Toolbox Reveals XRCC1 Deficiency–Driven Reshaping of the PARP1 Mono-ADP-Ribosylation Wave
Description	ADP-ribosylation has long been recognized as a key regulator of essential signaling pathways, including the DNA damage response. However, only recent and ongoing technological advances are beginning to make it possible to investigate its distinct forms with molecular precision. Here, we designed a ‘mono-ADP-ribosylation blocking’ strategy to develop sensitive, modular antibodies with high specificity for poly-ADP-ribosylation. During peptide antigen generation, we identified a distinctive mass spectrometric signature that enabled accurate mapping of poly- ADP-ribosylation sites and helped prevent site mislocalization. Moreover, we affinity-matured mono-ADP-ribosylation and histone H3 site-specific antibodies. These tools reveal that, upon DNA damage, XRCC1 deficiency dramatically elevates the mono-ADP-ribosylation wave of PARP1 signaling, in addition to increasing poly-ADP-ribosylation. This PARP1 hyperactivation leads to an increase in an unconventional form of ubiquitylation, recently shown to directly target mono- ADP-ribose in the DNA damage response and other signaling pathways. Consequently, XRCC1 loss enhanced the recruitment of RNF114, the reader of this composite modification, to DNA lesions. Our findings establish mono-ADP-ribosylation – and its downstream ubiquitylation – as a key modification triggered by XRCC1 deficiency during DNA damage, enabled by newly developed tools for precise and sensitive detection of ADP-ribosylation.
HostingRepository	PRIDE
AnnounceDate	2026-02-18
AnnouncementXML	Submission_2026-02-18_01:30:22.268.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilian Atanassov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 05:04:20	ID requested
⏵ 1	2026-02-18 01:30:22	announced

Dataset with its publication pending

submitter keyword: PARP1, ADP-Ribisylation

Ivan Matic
contact affiliation	Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
contact email	imatic@age.mpg.de
lab head
Ilian Atanassov
contact affiliation	Max Planck Institute for Biology of Aging
contact email	ilian.atanassov@age.mpg.de
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/2026/02/PXD066208

PRIDE project URI

• PRIDE
  1. PXD066208
     1. Label: PRIDE project
     2. Name: A Versatile Toolbox Reveals XRCC1 Deficiency–Driven Reshaping of the PARP1 Mono-ADP-Ribosylation Wave