Pathogenic PPM1D variants and their impact on DNA replication

Název projektu anglicky
Pathogenic PPM1D variants and their impact on DNA replication
Anotace anglicky
Upon DNA damage, cells protect genome integrity by activating ATM/ATR kinases that are master regulators of the coordinated recruitment of the repair factors to DNA lesions and of the cell cycle checkpoint. PPM1D phosphatase counteracts ATM/ATR activity at chromatin and terminates the checkpoint by inhibiting the tumor suppressor p53. We have recently identified gain-of-function mutations in the PPM1D that allow proliferation in the presence of DNA damage, promote genome instability and cellular transformation. How the C-terminally truncated PPM1D mutants escape the protein degradation remains currently unclear. Here, we aim to elucidate the mechanism of the rapid turnover of PPM1D in normal cells by the proteomic analysis of the interacting proteins with the C-terminal degron. Further, we will determine how the increased PPM1D activity affects DNA replication by targeting proteins directly at the replication forks and indirectly by suppressing p53 and other signaling pathways. This project will contribute to understanding the role of PPM1D in genomic instability and cancer.

Kategorie VaV
ZV - Základní výzkum
OECD FORD - hlavní obor
10608 - Biochemistry and molecular biology
OECD FORD - vedlejší obor
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OECD FORD - další vedlejší obor
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CEP - odpovídající obory <br>(dle <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">převodníku</a>)
CE - Biochemie<br>EB - Genetika a molekulární biologie

Důvěrnost údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Systémové označení dodávky dat
CEP26-GA0-GA-R
Datum dodání záznamu
27. 4. 2026

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