PXD069605

PXD069605 is an original dataset announced via ProteomeXchange.

Title	ID3 Deficiency Alters Chromatin Accessibility at DSB Sites and Enhances Vulnerability to HDAC Inhibition
Description	The inhibitor of DNA-binding 3 (ID3) plays a crucial role in DNA double-strand break (DSB) repair. We previously reported that ID3 loss reduced chromatin accessibility at DNA repair gene promoters, yet its exact role in DNA repair via chromatin regulation remained elusive. Using the AID-DIvA cell system with inducible DSBs, we show that ID3 directly regulates chromatin accessibility at DSB sites, as demonstrated by reduced chromatin accessibility and lower H3K27ac levels in ID3-knockout (KO) cells. Loss of ID3 renders cells highly sensitive to histone deacetylase (HDAC) inhibition, particularly to the Class I HDAC inhibitor, leading to the accumulation of unrepaired DSBs and delayed cell cycle progression. Transcriptome and proteome analyses revealed that HDAC inhibition in ID3-KO cells results in the downregulation of gene sets involved in the regulation of cell cycle and cell division. The synthetic lethality observed between ID3 loss and Class I HDAC inhibition underscores a novel therapeutic vulnerability in ID3-deficient cancers, driven by compounded defects in chromatin remodeling, cell cycle, and DNA repair. Our study provides new insights into the relationship between chromatin regulation and genome stability, with implications for targeted cancer therapies.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_17:17:17.254.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gianluca Sigismondo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-17 15:58:31	ID requested
⏵ 1	2026-05-24 17:17:18	announced

10.1002/ijc.70400;

Corte GD, Eldesouky H, Puchan J, Ö, z S, Everatt E, Goyal A, Sigismondo G, Oppermann U, Plass C, Weichenhan D, Bakr A, ID3 deficiency alters chromatin accessibility at DSB sites and enhances vulnerability to HDAC inhibition. Int J Cancer, 158(12):3173-3186(2026) [pubmed]

submitter keyword: ID3, chromatin accessibility, HDAC, DSB, inhibition

Ali Bakr
contact affiliation	German Cancer Research Center (DKFZ), Division of Cancer Epigenomics
contact email	a.bakr@dkfz.de
lab head
Gianluca Sigismondo
contact affiliation	DKFZ
contact email	gianluca.sigismondo@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/2026/05/PXD069605

PRIDE project URI

• PRIDE
  1. PXD069605
     1. Label: PRIDE project
     2. Name: ID3 Deficiency Alters Chromatin Accessibility at DSB Sites and Enhances Vulnerability to HDAC Inhibition