Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.

ABSTRACT: In response to DNA double strand breaks, the histone variant H2AX at the break site is phosphorylated at serine 139 by DNA damage sensor kinases such as ataxia telangiectasia-mutated, forming gamma-H2AX. This phosphorylation event is critical for sustained recruitment of other proteins to repair the break. After repair, restoration of the cell to a prestress state is associated with gamma-H2AX dephosphorylation and dissolution of gamma-H2AX-associated damage foci. The phosphatases PP2A and PP4 have previously been shown to dephosphorylate gamma-H2AX. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (WIP1) also dephosphorylates gamma-H2AX at serine 139 in vitro and in vivo. Overexpression of WIP1 reduces formation of gamma-H2AX foci in response to ionizing and ultraviolet r

SUBMITTER: Moon SH 

PROVIDER: S-EPMC2857113 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature