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Signaling of DNA Replication Stress Through the ATR Checkpoint

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DNA Replication, Recombination, and Repair

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Abstract

DNA replication is one of the most fundamental cellular processes. Faithful replication of the entire genome is a daunting task, especially when cells are under intrinsic or extrinsic stress. To maintain genomic stability during DNA replication, eukaryotic cells have evolved a sophisticated signaling network called the checkpoint to orchestrate cellular responses to different types of DNA replication problems. The ATR kinase is the master regulator of the DNA replication checkpoint. Activated by a wide spectrum of DNA damage and replication problems, ATR and its effector kinase Chk1 regulate and coordinate DNA replication, DNA repair, and cell cycle transitions. Mounting evidence has suggested that the ATR checkpoint pathway is crucial for the suppression of genomic instability and sustained cell survival. In this review, we will discuss the recent findings on how the ATR pathway is activated by replication stress and how this pathway functions to suppress genomic instability during DNA replication.

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Acknowledgment

We apologize to the colleagues whose work is not cited in this article due to space limitation. B. S. is supported by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KAKENHI, 25701005). L. Z. is a Jim & Ann Orr Massachusetts General Hospital Research Scholar and is supported by grants from NIH (GM076388) and the Federal Share of MGH Proton Program.

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  1. Division of Genetics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan

    Bunsyo Shiotani

  2. Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA

    Lee Zou

  3. Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA

    Lee Zou

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  1. Bunsyo Shiotani
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  2. Lee Zou
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Correspondence to Bunsyo Shiotani or Lee Zou .

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  1. Dept of Life Sci, Faculty of Sci., Gakushuin University, Toshima, Tokyo, Japan

    Fumio Hanaoka

  2. Biosignal Research Center, Kobe University, Kobe, Japan

    Kaoru Sugasawa

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Shiotani, B., Zou, L. (2016). Signaling of DNA Replication Stress Through the ATR Checkpoint. In: Hanaoka, F., Sugasawa, K. (eds) DNA Replication, Recombination, and Repair. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55873-6_16

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