γ-H2AX Dephosphorylation by Protein Phosphatase 2A Facilitates DNA Double-Strand Break Repair
2005; Elsevier BV; Volume: 20; Issue: 5 Linguagem: Inglês
10.1016/j.molcel.2005.10.003
ISSN1097-4164
AutoresDipanjan Chowdhury, Michael‐Christopher Keogh, Haruhiko Ishii, Craig L. Peterson, Stephen Buratowski, Judy Lieberman,
Tópico(s)Carcinogens and Genotoxicity Assessment
ResumoPhosphorylated histone H2AX (γ-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 γ-H2AX is removed from chromatin remains unknown. Here, we show that protein phosphatase 2A (PP2A) is involved in removing γ-H2AX foci. The PP2A catalytic subunit [PP2A(C)] and γ-H2AX coimmunoprecipitate and colocalize in DNA damage foci and PP2A dephosphorylates γ-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, γ-H2AX foci persist, DNA repair is inefficient, and cells are hypersensitive to DNA damage. The effect of PP2A on γ-H2AX levels is independent of ATM, ATR, or DNA-PK activity.
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