γ-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair

被引：440

作者：

Chowdhury, D

Keogh, MC

Ishii, H

Peterson, CL

Buratowski, S

Lieberman, J ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[4] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA

来源：

MOLECULAR CELL | 2005年 / 20卷 / 05期

关键词：

D O I：

10.1016/j.molcel.2005.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphorylated histone H2AX (gamma-H2AX) forms foci over large chromatin domains surrounding double-stranded DNA breaks (DSB). These foci recruit DSB repair proteins and dissolve during or after repair is completed. How gamma-H2AX is removed from chromatin remains unknown. Here, we show that protein phosphatase 2A (PP2A) is involved in removing gamma-H2AX foci. The PP2A catalytic subunit [PP2A(C)] and gamma-H2AX communoprecipitate and colocalize in DNA damage foci and PP2A dephosphorylates gamma-H2AX in vitro. The recruitment of PP2A(C) to DNA damage foci is H2AX dependent. When PP2A(C) is inhibited or silenced by RNA interference, gamma-H2AX foci persist, DNA repair is inefficient, and cells are hypersensitive to DNA damage. The effect of PP2A on gamma-H2AX levels is independent of ATM, ATR, or DNA-PK activity.

引用

页码：801 / 809

页数：9

共 43 条

[1] DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].