WIP1 Promotes Homologous Recombination and Modulates Sensitivity to PARP Inhibitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00521713" target="_blank" >RIV/68378050:_____/19:00521713 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2073-4409/8/10/1258" target="_blank" >https://www.mdpi.com/2073-4409/8/10/1258</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells8101258" target="_blank" >10.3390/cells8101258</a>

Result language

angličtina

Original language name

WIP1 Promotes Homologous Recombination and Modulates Sensitivity to PARP Inhibitors

Original language description

Genotoxic stress triggers a combined action of DNA repair and cell cycle checkpoint pathways. Protein phosphatase 2C delta (referred to as WIP1) is involved in timely inactivation of DNA damage response by suppressing function of p53 and other targets at chromatin. Here we show that WIP1 promotes DNA repair through homologous recombination. Loss or inhibition of WIP1 delayed disappearance of the ionizing radiation-induced 53BP1 foci in S/G2 cells and promoted cell death. We identify breast cancer associated protein 1 (BRCA1) as interactor and substrate of WIP1 and demonstrate that WIP1 activity is needed for correct dynamics of BRCA1 recruitment to chromatin flanking the DNA lesion. In addition, WIP1 dephosphorylates 53BP1 at Threonine 543 that was previously implicated in mediating interaction with RIF1. Finally, we report that inhibition of WIP1 allowed accumulation of DNA damage in S/G2 cells and increased sensitivity of cancer cells to a poly-(ADP-ribose) polymerase inhibitor olaparib. We propose that inhibition of WIP1 may increase sensitivity of BRCA1-proficient cancer cells to olaparib.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

10

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

1258

UT code for WoS article

000497336400147

EID of the result in the Scopus database

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