Počet záznamů: 1
Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition
0354924 - UMG-J 2011 RIV GB eng J - Článek v odborném periodiku
Macůrek, Libor - Lindqvist, A. - Voets, O. - Kool, J. - Vos, H.R. - Medema, R.H.
Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition.
Oncogene. Roč. 29, č. 15 (2010), s. 2281-2291 ISSN 0950-9232
Grant CEP: GA ČR GPP305/10/P420
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: DNA damage * checkpoint * phosphatase
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 7.414, rok: 2010
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 retention of 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 depleted of 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 plays an essential role in dephosphorylation of gamma-H2AX in order to silence the checkpoint and restore chromatin structure once DNA damage is repaired.
Trvalý link: http://hdl.handle.net/11104/0193819