Mechanisms of Non-canonical Activation of Ataxia Telangiectasia Mutated

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Updated: Mar 6, 2026

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration
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Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration

Published on: December 27, 2024

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S V Khoronenkova1

  • 1University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, UK. sk870@cam.ac.uk.

Biochemistry. Biokhimiia
|March 7, 2017
PubMed

Insights

The ATM protein, crucial for DNA damage response, can be activated through novel pathways beyond double-strand breaks. These non-canonical mechanisms involve cytoskeletal changes and RNA-DNA hybrids, potentially impacting Ataxia Telangiectasia.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The ATM (Ataxia Telangiectasia Mutated) kinase is a central regulator of cellular responses to DNA damage.
  • Classical ATM activation occurs via monomerization following DNA double-strand breaks, initiating downstream signaling cascades.
  • ATM controls numerous substrates involved in cell cycle arrest, DNA repair, and apoptosis.

Purpose of the Study:

  • To review emerging evidence for non-canonical ATM activation pathways.
  • To explore stimuli distinct from DNA double-strand breaks that trigger ATM.
  • To discuss the potential relevance of these non-canonical pathways in Ataxia Telangiectasia.

Main Methods:

  • Review of recent experimental findings on ATM activation.
  • Analysis of studies investigating stimuli beyond DNA double-strand breaks.
  • Integration of data linking non-canonical ATM activation to cellular processes.

Main Results:

  • ATM activation can be induced by stimuli other than DNA double-strand breaks.
  • Identified non-canonical activators include cytoskeletal alterations, chromatin modifications, RNA-DNA hybrids, and DNA single-strand breaks.
  • These alternative activation routes highlight the complexity of ATM signaling.

Conclusions:

  • ATM exhibits versatile activation mechanisms beyond the classical DNA double-strand break pathway.
  • Non-canonical ATM activation pathways represent a significant area for future research.
  • Understanding these pathways may offer new insights into the pathology of Ataxia Telangiectasia and related disorders.

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