The mTOR pathway: Implications for DNA replication

Noa Lamm; Samuel Rogers; Anthony J Cesare

doi:10.1016/j.pbiomolbio.2019.04.002

The mTOR pathway: Implications for DNA replication

Prog Biophys Mol Biol. 2019 Oct:147:17-25. doi: 10.1016/j.pbiomolbio.2019.04.002. Epub 2019 Apr 13.

Authors

Noa Lamm¹, Samuel Rogers¹, Anthony J Cesare²

Affiliations

¹ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, 2145, Australia.
² Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, 2145, Australia. Electronic address: tcesare@cmri.org.au.

PMID: 30991055
DOI: 10.1016/j.pbiomolbio.2019.04.002

Abstract

DNA replication plays a central role in genome health. Deleterious alteration of replication dynamics, or "replication stress", is a key driver of genome instability and oncogenesis. The replication stress response is regulated by the ATR kinase, which functions to mitigate replication abnormalities through coordinated efforts that arrest the cell cycle and repair damaged replication forks. mTOR kinase regulates signaling networks that control cell growth and metabolism in response to environmental cues and cell stress. In this review, we discuss interconnectivity between the ATR and mTOR pathways, and provide putative mechanisms for mTOR engagement in DNA replication and the replication stress response. Finally, we describe how connectivity between mTOR and replication stress may be exploited for cancer therapy.

Keywords: ATR; DNA replication; Genome stability; Replication stress; mTOR.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
DNA Damage
DNA Replication*
Humans
TOR Serine-Threonine Kinases / metabolism*

Substances

TOR Serine-Threonine Kinases