PXD035268

PXD035268 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) is involved in termination of the cell cycle checkpoint by counteracting activity of the tumour suppressor protein p53. By dephosphorylating various proteins at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified interaction between PPM1D and the components of the shelterin complex that protects telomeric DNA. Interaction between PPM1D and TRF2 was confirmed by immunoprecipitation and proximity ligation assay. Confocal microscopy revealed colocalisation of the endogenous PPM1D with TRF2 at telomeres. Further, we found that TRF2 was phosphorylated by ATR at S410 after induction of DNA damage at telomeres and this modification was increased in cells lacking PPM1D or after PPM1D inhibition. Phosphorylation of TRF2 stimulated its interaction with TIN2 at telomeres and in vitro. Conversely, overexpression of PPM1D impaired localisation of TIN2 at telomeres. Finally, inhibition of PPM1D impaired recruitment of 53BP1 and RAD51 to DNA double strand breaks at telomeres. Expression of TRF2-S410A mutant fully rescued the recruitment of 53BP1 to telomeric breaks. These results suggest that TRF2 phosphorylation promotes association of TIN2 with the shelterin complex and regulates DNA repair at telomeres.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:38:25.902.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Talacko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-11 15:05:06	ID requested
1	2023-03-10 23:30:53	announced
⏵ 2	2023-11-14 08:38:26	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, DNA repair,PPM1D, DNA damage response

Libor Macurek
contact affiliation	Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences Vídeňská 1083, 142 20 Prague 4, Czech Republic
contact email	macurek@img.cas.cz
lab head
Pavel Talacko
contact affiliation	BIOCEV, Faculty of Science, Charles University in Prague
contact email	pavel.talacko@natur.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035268
     1. Label: PRIDE project
     2. Name: Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA repair at damaged telomeres