PXD035273

PXD035273 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA repair at damaged telomeres.
Description	Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. By targeting additional substrates at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified a novel interaction between PPM1D and the shelterin complex that protects telomeric DNA. In addition, confocal microscopy revealed that endogenous PPM1D colocalized with TRF2 at telomeres. Further, we found that ATR phosphorylated TRF2 at S410 after induction of DNA double strand breaks at telomeres and this modification increased after inhibition or loss of PPM1D. TRF2 phosphorylation stimulated its interaction with TIN2 both in vitro and at telomeres. Conversely, induced expression of PPM1D impaired localisation of TIN2 and TPP1 at telomeres. Finally, recruitment of the DNA repair factor 53BP1 to the telomeric breaks was strongly reduced after inhibition of PPM1D and was rescued by the expression of TRF2-S410A mutant. Our results suggest that TRF2 phosphorylation promotes the association of TIN2 within the shelterin complex and regulates DNA repair at telomeres.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:38:10.310.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-11 15:31:50	ID requested
1	2023-03-10 23:16:19	announced
⏵ 2	2023-11-14 08:38:12	announced	2023-11-14: Updated project metadata.

Storchova R, Palek M, Palkova N, Veverka P, Brom T, Hofr C, Macurek L, Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres. Nucleic Acids Res, 51(3):1154-1172(2023) [pubmed]

submitter keyword: TRF2, shelterin, telomere, phosphorylation,PPM1D phosphatase

dr. Libor Macurek
contact affiliation	Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
contact email	libor.macurek@img.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	maralab@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/2023/03/PXD035273

PRIDE project URI

• PRIDE
  1. PXD035273
     1. Label: PRIDE project
     2. Name: Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA repair at damaged telomeres.