PXD027421

PXD027421 is an original dataset announced via ProteomeXchange.

Title	Multi-layered chromatin proteomics identifies cell vulnerabilities in DNA repair
Description	DNA damage response (DDR) is instrumental for maintaining genome stability and its deregulation predisposes to carcinogenesis, while revealing attractive targets for innovative therapies. Chromatin governs the DNA repair process via the interplay among different layers consisting of DNA, histones post-translational modifications (hPTMs), and chromatin-associated proteins. Here we employ multi-layered proteomics to follow, during double-strand break repair, chromatin-mediated interactions of repair proteins, signatures of hPTMs, and the DNA-bound proteome. In particular, we functionally attribute novel chromatin-associated proteins to non-homologous end-joining or homologous recombination (HR) repair, we reveal susceptibility to PARP inhibitor treatment upon knockdown of ATAD2, TPX2 and EHMT2, and we profile hPTMs at γH2AX-mononucleosomes. Moreover, through the integration of these multiple chromatin layers we identify a potential role for EHMT2-mediated monomethylation of H3K56 in HR. Collectively, our results provide an innovative chromatin-centered view of the DDR process, while representing a valuable resource for the use of PARP inhibitors in cancer.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:34.222.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	monomethylated residue; biotinylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-19 09:00:26	ID requested
1	2023-02-20 08:49:49	announced
⏵ 2	2023-11-14 08:32:35	announced	2023-11-14: Updated project metadata.

Sigismondo G, Arseni L, Palacio-Escat N, Hofmann TG, Seiffert M, Krijgsveld J, Multi-layered chromatin proteomics identifies cell vulnerabilities in DNA repair. Nucleic Acids Res, 51(2):687-711(2023) [pubmed]

submitter keyword: proteomics, hPTMs, iPOC, ChIP-SICAP, DNA damage foci,chromatin, DSB, DDR

Jeroen Krijgsveld
contact affiliation	Division of Proteomics of Stem Cells and Cancer
contact email	j.krijgsveld@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/2023/02/PXD027421

PRIDE project URI

• PRIDE
  1. PXD027421
     1. Label: PRIDE project
     2. Name: Multi-layered chromatin proteomics identifies cell vulnerabilities in DNA repair