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Molecular Insights into the Regulation of Apoptosis and Cellular Senescence and Their Implications for Cancer

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DNA Replication, Recombination, and Repair

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Abstract

Eukaryotic cells continuously encounter DNA damage caused by uncontrolled DNA replication and several sources of genotoxic stresses such as ultraviolet or ionizing irradiation. The cells have acquired the surveillance system, known as the DNA damage responses, to maintain genomic integrity. The DNA damage responses play an important role in sensing DNA damage, transmitting the signals to downstream targets, and coordinating various cellular responses such as cell-cycle arrest, apoptosis, and cellular senescence. Apoptosis is a highly regulated cell death process that controls cellular homeostasis and prevents survival of injured, damaged, or transformed cells. On the other hand, cellular senescence is not only a potent tumor-suppressive mechanism leading to permanent cell-cycle arrest but also is proposed to drive organismal aging. Recent advances in understanding the molecular mechanisms that regulate apoptosis and cellular senescence identified various key regulators. In this chapter, we will review the signaling networks underlying the induction of apoptosis and cellular senescence and their implications for cancer development and therapy. We will also discuss cellular senescence’s impact beyond the tumor-suppressive function, animal aging, and tissue homeostasis.

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Acknowledgments

We are grateful to Dr. Keiko Kono for critically reading the manuscript and all of the members of Nakanishi’s laboratory for useful discussions during the preparation of this manuscript. We also regret not being able to cite all the major contributions to this field and those colleagues whose work we should have cited but inadvertently did not. M.N. was supported by a Grants-in-Aid for Scientific Research on Innovative Areas, “Cell Fate Control”; Scientific Research (A); and Challenging Exploratory Research from MEXT, Japan.

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  1. Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Yoshikazu Johmura & Makoto Nakanishi

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  1. Yoshikazu Johmura
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  2. Makoto Nakanishi
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Correspondence to Makoto Nakanishi .

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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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Johmura, Y., Nakanishi, M. (2016). Molecular Insights into the Regulation of Apoptosis and Cellular Senescence and Their Implications for Cancer. In: Hanaoka, F., Sugasawa, K. (eds) DNA Replication, Recombination, and Repair. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55873-6_18

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