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The ATM protein: the importance of being active

Yosef Shiloh1, Yael Ziv

  • 1The David and Inez Myers Laboratory for Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. yossih@post.tau.ac.il

The Journal of Cell Biology
|August 8, 2012
PubMed

Insights

A catalytically inactive ATM protein kinase causes embryonic lethality in mice, a surprising finding given the moderate phenotype of ATM-deficient mice. This impacts DNA damage response research and cancer therapeutics.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • The ataxia telangiectasia mutated (ATM) protein kinase is crucial for the cellular response to DNA double-strand breaks.
  • ATM phosphorylates key proteins within the DNA damage response network.

Purpose of the Study:

  • To investigate the in vivo role of ATM's catalytic activity in embryonic development.
  • To compare the phenotype of mice with a catalytically inactive ATM to those lacking ATM entirely.

Main Methods:

  • Generation of mice expressing a catalytically inactive ATM protein.
  • Phenotypic analysis of these mice during embryonic development.
  • Comparison with existing data from ATM-deficient mouse models.

Main Results:

  • Mice expressing a catalytically inactive ATM exhibited embryonic lethality.
  • This outcome was unexpected, as ATM-deficient mice display a less severe phenotype.
  • The catalytic activity of ATM is essential for embryonic survival.

Conclusions:

  • The catalytic function of ATM is indispensable for embryonic development in mice.
  • These findings necessitate a re-evaluation of ATM's role in DNA repair and organismal development.
  • Implications for understanding ATM-related disorders and developing targeted cancer therapies.

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