期刊
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
卷 147, 期 -, 页码 17-25出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2019.04.002
关键词
DNA replication; Replication stress; mTOR; ATR; Genome stability
资金
- Cancer Institute NSW
- Australian NHMRC [1106241, 1104461, 1162886]
- Goodridge Foundation
- Sydney West Radiation Oncology Network
- National Health and Medical Research Council of Australia [1162886, 1104461, 1106241] Funding Source: NHMRC
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. (C) 2019 The Authors. Published by Elsevier Ltd.
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