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The mTOR pathway: Implications for DNA replication

Noa Lamm1, Samuel Rogers1, Anthony J Cesare1

  • 1Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, 2145, Australia.

Progress in Biophysics and Molecular Biology
|April 17, 2019
PubMed

Insights

The ATR and mTOR pathways are interconnected, influencing DNA replication and stress responses. Understanding this link may reveal new cancer treatment strategies targeting replication stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • DNA replication is crucial for genome stability.
  • Replication stress, an alteration in DNA replication dynamics, drives genome instability and cancer.
  • The ATR kinase regulates the replication stress response to maintain genome integrity.

Purpose of the Study:

  • To review the interconnectivity between the ATR and mTOR kinase pathways.
  • To explore potential mechanisms of mTOR involvement in DNA replication and the replication stress response.
  • To discuss the therapeutic potential of targeting the mTOR-replication stress axis in cancer.

Main Methods:

  • Literature review of existing research on ATR, mTOR, DNA replication, and cancer.
  • Analysis of signaling networks and molecular mechanisms.
  • Synthesis of current knowledge to propose putative interactions.

Main Results:

  • The ATR and mTOR pathways exhibit significant interconnectivity.
  • mTOR signaling influences cell growth, metabolism, and stress responses, potentially impacting DNA replication.
  • Evidence suggests mTOR plays a role in managing replication stress.

Conclusions:

  • The interplay between ATR and mTOR is critical for regulating DNA replication and cellular responses to stress.
  • Targeting the connection between mTOR and replication stress offers a promising avenue for novel cancer therapies.
  • Further research into these pathways could lead to improved oncological treatments.
Keywords:
ATRDNA replicationGenome stabilityReplication stressmTOR

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