PXD047225

PXD047225 is an original dataset announced via ProteomeXchange.

Title	ARID1A regulates chromatin organization and establishment of epigenetic marks for DSB repair and transcription silencing
Description	AT-rich interactive domain-containing protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. ARID1A contributes to DNA damage response pathways, and we previously reported that ARID1A loss is associated with mutational signatures linked to DNA repair defects. Here we show that ARID1A is promoting both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates the chromatin loop formation at DSB sites by interacting with the cohesin subunit RAD21 and CTCF insulator protein promoting their enrichment around the DSBs. Further analysis demonstrates that ARID1A’s involvement in DSB repair is accompanied by alterations of chromatin accessibility and distribution of activating histone marks at DSBs. ARID1A binds to and promotes the recruitment of the HDAC1 to control transcription repression at these DSBs. Altogether, ARID1A simultaneously regulates DSB repair and transcription silencing in transcriptionally active chromatin. ARID1A depletion resulted in defective DSB repair, which subsequently led to accumulation of micronuclei, activation of cGAS-STING pathway and an increased expression of immunomodulatory cytokines and chemokines upon IR treatment. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and can estimate the levels of tumor-infiltrating immune cells and response to combination of radio- and immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2024-06-22
AnnouncementXML	Submission_2024-06-22_08:36:17.197.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	2023-11-24 08:40:33	ID requested
⏵ 1	2024-06-22 08:36:18	announced

Bakr A, Corte GD, Veselinov O, Kelek, ç, i S, Chen MM, Lin YY, Sigismondo G, Iacovone M, Cross A, Syed R, Jeong Y, Sollier E, Liu CS, Lutsik P, Krijgsveld J, Weichenhan D, Plass C, Popanda O, Schmezer P, ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response. Nucleic Acids Res, 52(10):5698-5719(2024) [pubmed]

10.1093/nar/gkae233;

submitter keyword: DSB repair, epigenetic regulation,ARID1A, chromatin

Peter Schmezer1
contact affiliation	Division of Cancer Epigenomics, German Cancer Research Center (DKFZ)
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/2024/06/PXD047225

PRIDE project URI

• PRIDE
  1. PXD047225
     1. Label: PRIDE project
     2. Name: ARID1A regulates chromatin organization and establishment of epigenetic marks for DSB repair and transcription silencing