Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation

Ambereen Ali1, Ji Zhang, Shideng Bao

  • 1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Genes & Development
|February 12, 2004
PubMed

Insights

Protein phosphatase 5 (PP5) directly regulates ATM activation following DNA double-strand breaks. PP5 is essential for ATM

Area of Science:

  • Cellular biology
  • Molecular oncology
  • DNA damage response

Background:

  • ATM (Ataxia-telangiectasia mutated) is a key kinase in DNA double-strand break repair.
  • ATM activation mechanisms under genotoxic stress require further elucidation.

Purpose of the Study:

  • To investigate the role of protein phosphatase 5 (PP5) in ATM activation.
  • To elucidate the regulatory linkage between PP5 and ATM signaling.

Main Methods:

  • Investigated PP5-ATM interaction using co-immunoprecipitation.
  • Assessed ATM activation and substrate phosphorylation via Western blotting.
  • Analyzed cell-cycle checkpoint function using flow cytometry.

Main Results:

  • PP5 interacts with ATM in a DNA-damage-dependent manner.
  • Reduced PP5 expression impairs ATM activation and autophosphorylation at Ser1981.
  • Inactive PP5 mutant expression disrupts ATM substrate phosphorylation and causes S-phase checkpoint defects.

Conclusions:

  • PP5 is a crucial regulator of ATM activation and function.
  • PP5 plays an essential role in ATM-mediated DNA damage checkpoint signaling.

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