Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00570596" target="_blank" >RIV/68378050:_____/23:00570596 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/23:00130227
Result on the web
<a href="https://academic.oup.com/nar/article/51/3/1154/6991041" target="_blank" >https://academic.oup.com/nar/article/51/3/1154/6991041</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkac1269" target="_blank" >10.1093/nar/gkac1269</a>

Result language
angličtina
Original language name
Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres
Original language 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 localises 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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