Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F10%3A00354924" target="_blank" >RIV/68378050:_____/10:00354924 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition

Popis výsledku v původním jazyce

DNA double-stranded breaks (DSBs) elicit a checkpoint response that causes a delay in cell cycle progression and enables DNA repair. Phosphorylated form of the histone H2AX (called gamma-H2AX) serves as an essential platform for recruitment and retentionof additional components of the checkpoint signaling cascade (such as MDC1 and 53BP1) in the chromatin region flanking the DSB. Here we demonstrate that the Wip1 phosphatase is bound to chromatin and directly dephosphorylates gamma-H2AX. Cells depletedof Wip1 fail to dephosphorylate gamma-H2AX during checkpoint recovery. Conversely, premature activation of Wip1 leads to displacement of MDC1 from damage foci and prevents activation of the checkpoint. Taken together, our data demonstrate that Wip1 playsan essential role in dephosphorylation of gamma-H2AX in order to silence the checkpoint and restore chromatin structure once DNA damage is repaired.

Název v anglickém jazyce

Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition

Popis výsledku anglicky

DNA double-stranded breaks (DSBs) elicit a checkpoint response that causes a delay in cell cycle progression and enables DNA repair. Phosphorylated form of the histone H2AX (called gamma-H2AX) serves as an essential platform for recruitment and retentionof additional components of the checkpoint signaling cascade (such as MDC1 and 53BP1) in the chromatin region flanking the DSB. Here we demonstrate that the Wip1 phosphatase is bound to chromatin and directly dephosphorylates gamma-H2AX. Cells depletedof Wip1 fail to dephosphorylate gamma-H2AX during checkpoint recovery. Conversely, premature activation of Wip1 leads to displacement of MDC1 from damage foci and prevents activation of the checkpoint. Taken together, our data demonstrate that Wip1 playsan essential role in dephosphorylation of gamma-H2AX in order to silence the checkpoint and restore chromatin structure once DNA damage is repaired.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/GPP305%2F10%2FP420" target="_blank" >GPP305/10/P420: Role Wip1 fosfatázy v buněčné odpovědi na poškození DNA</a><br>

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

Oncogene

ISSN

0950-9232

e-ISSN

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Svazek periodika

29

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

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Kód UT WoS článku

000276685200013

EID výsledku v databázi Scopus

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