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Roles of ATM and ATR in DNA double strand breaks and replication stress

Rhys M Williams1, Xiaodong Zhang1

  • 1Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London, SW7 2AZ, UK.

Progress in Biophysics and Molecular Biology
|April 22, 2021
PubMed

Insights

Genome integrity is maintained by ATM and ATR kinases, which respond differently to DNA damage and replication stress. Controlling their localization orchestrates stress-specific DNA repair pathways.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Genome integrity is crucial for cell division and preventing DNA damage accumulation, which can lead to cancer.
  • ATM (Ataxia-Telangiectasia Mutated) and ATR (Ataxia-Telangiectasia and Rad3-Related) are key kinases involved in DNA repair.
  • These kinases play intertwined roles in repairing double-strand breaks but diverge in response to replication stress.

Purpose of the Study:

  • To review the current understanding of ATM and ATR kinase roles in DNA damage and replication stress response.
  • To elucidate the mechanisms of ATM and ATR recruitment, activation, and activity.
  • To discuss how kinase localization controls stress-specific responses.

Main Methods:

  • Literature review of studies on ATM and ATR signaling pathways.
  • Analysis of molecular mechanisms governing kinase recruitment and activation.
  • Comparative analysis of ATM and ATR roles in different cellular stress conditions.

Main Results:

  • ATM and ATR are essential for homologous recombination repair and preventing genome instability.
  • Their functions are interconnected in double-strand break repair but distinct during replication stress.
  • Kinase localization is a critical factor in orchestrating specific cellular responses to DNA damage and replication stress.

Conclusions:

  • ATM and ATR kinases are central regulators of genome maintenance.
  • Understanding their distinct roles and localization dynamics is key to comprehending cellular responses to DNA damage and replication stress.
  • This knowledge may inform strategies for cancer therapy.
Keywords:
DNA damage SignallingHomologous recombinationPIKKsProtein kinasesRegulationReplication stress

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