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Updated: Jun 13, 2026

Quantification of γH2AX Foci in Response to Ionising Radiation
06:53

Quantification of γH2AX Foci in Response to Ionising Radiation

Published on: April 6, 2010

Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response

Hyukjin Cha1, Julie M Lowe, Henghong Li

  • 1Department of Biochemistry, Georgetown University, Washington, District of Columbia 20057-1468, USA. hjcha@cha.ac.kr

Cancer Research
|May 13, 2010
PubMed

Insights

Wild-type p53-induced phosphatase 1 (Wip1) dephosphorylates gamma-H2AX, a key marker in DNA damage response. Wip1

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Cellular DNA integrity is crucial for survival, facing constant threats from endogenous and exogenous sources.
  • The DNA damage response (DDR) involves histone modifications like gamma-H2AX phosphorylation to signal and repair DNA damage.
  • Dephosphorylation of gamma-H2AX is essential for timely DDR attenuation and genomic stability.

Purpose of the Study:

  • To investigate the role of wild-type p53-induced phosphatase 1 (Wip1) in gamma-H2AX dephosphorylation.
  • To determine the functional consequences of Wip1-mediated gamma-H2AX dephosphorylation on DNA repair.
  • To explore Wip1's function within the tumor surveillance network.

Main Methods:

  • In vitro and in vivo assays to assess Wip1 phosphatase activity on gamma-H2AX.
  • Experimental manipulation of Wip1 expression (ectopic expression and deletion) in cells exposed to ionizing and UV radiation.
  • Analysis of DNA repair factor recruitment to damage sites and assessment of DNA repair kinetics.

Main Results:

  • Wip1 effectively dephosphorylates gamma-H2AX both in vitro and in vivo.
  • Ectopic Wip1 expression reduces gamma-H2AX levels post-irradiation, while Wip1 deletion enhances gamma-H2AX accumulation under oncogenic stress.
  • Premature dephosphorylation of gamma-H2AX by Wip1 impairs DNA repair factor recruitment and delays DNA repair.

Conclusions:

  • Wip1 is a significant mammalian phosphatase for gamma-H2AX.
  • Wip1 influences DNA repair dynamics by regulating gamma-H2AX levels.
  • Wip1 contributes to tumor surveillance through its role in managing DNA damage signaling.

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