Role of the R2TP complex in response to DNA damage and cell cycle regulation View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2014-2018

FUNDING AMOUNT

6165000 CZK

ABSTRACT

The ATM, ATR and DNA-PKc kinases play a key role in cellular response to DNA damage and genome integrity control. Their stability is regulated by the R2TP complex, which controls the formation of large protein complexes. The R2T of the PIH1D1 complex is shown to be a novel phosphorylated substrate binding protein and its activity is essential for the R2TP function. To confirm this concept, we used a proteomic and in silico approach to search for new phospho-binding partners R2TP. Among other things, we identified cell cycle regulating proteins and response to DNA damage and confirmed a direct linkage between PIH1D1 and the phosphorylated ECD protein that regulates the stabilization of the p53 tumor suppressor. In this project, we want to study the mechanism by which R2TP regulates the stabilization of p53 in response to DNA damage and the consequences of this regulation for the cell cycle. At the same time, we will study how R2TP components control the response to damaged DNA through our identified binding partners. This work will bring new findings on cell cycle regulation and cellular response to DNA damage by the R2TP complex. More... »

URL

https://www.rvvi.cz/cep?s=jednoduche-vyhledavani&ss=detail&n=0&h=GA14-34264S

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