PXD028946

PXD028946 is an original dataset announced via ProteomeXchange.

Title	ID3 Promotes Homologous Recombination via Non-transcriptional and Transcriptional Mechanisms and its Loss Confers Sensitivity to PARP Inhibition
Description	The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-16_23:34:52.140.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: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-05 02:00:48	ID requested
⏵ 1	2022-02-16 23:34:52	announced

Bakr A, Hey J, Sigismondo G, Liu CS, Sadik A, Goyal A, Cross A, Iyer RL, M, ü, ller P, Trauernicht M, Breuer K, Lutsik P, Opitz CA, Krijgsveld J, Weichenhan D, Plass C, Popanda O, Schmezer P, ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition. Nucleic Acids Res, 49(20):11666-11689(2021) [pubmed]

submitter keyword: ID3, DSBs, DNA repair, HR, PARPi, cell sensitivity

Peter Schmezer
contact affiliation	Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), INF280, 69120 Heidelberg, Germany
contact email	p.schmezer@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/2022/02/PXD028946

PRIDE project URI

• PRIDE
  1. PXD028946
     1. Label: PRIDE project
     2. Name: ID3 Promotes Homologous Recombination via Non-transcriptional and Transcriptional Mechanisms and its Loss Confers Sensitivity to PARP Inhibition