Abstract
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 coimmunoprecipitate 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / metabolism
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Cell Line
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DNA Damage*
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DNA Repair*
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DNA-Activated Protein Kinase / metabolism
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DNA-Binding Proteins / metabolism
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Fibroblasts
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HeLa Cells
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Histones / deficiency
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Histones / metabolism*
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Humans
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In Vitro Techniques
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Mice
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Phosphoprotein Phosphatases / metabolism*
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Phosphorylation
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Protein Phosphatase 2
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Protein Serine-Threonine Kinases / metabolism
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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H2AX protein, human
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Histones
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Tumor Suppressor Proteins
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gamma-H2AX protein, mouse
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Atr protein, mouse
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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DNA-Activated Protein Kinase
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Protein Serine-Threonine Kinases
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Phosphoprotein Phosphatases
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Protein Phosphatase 2