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Overview of the DNA Damage Checkpoint

ATM and ATR

  • Chapter
Apoptosis, Senescence, and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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summary

Maintenance of genome stability in response to DNA damage is essential for cell survival. DNA damage occurs following external insults such as ultraviolet light and ionizing radiations or as a consequence of DNA replication or physiological DNA rearrangements. Cells respond to DNA damage by the coordinated induction of cell-cycle arrest and DNA repair or trigger apoptosis if the damage is too extensive. The DNA damage response is induced by two prominent intermediates: double-strand breaks and single-strand DNA. These pathways are well conserved from yeast to mammals and comprise a network of proteins acting together to monitor, sense, and repair DNA damage. In this review, we will focus on the central role played by two protein kinases, Ataxia-Telangiectasia mutated (ATM) and ATM related (ATR), during S-phase checkpoints and how these proteins are regulated by other components of the DNA damage response such as BRCA1, the Mre11-Rad50-Nbs1 complex, Claspin, and ATR-interacting protein (ATRIP). All these proteins, which are involved in sensing the damage (ATM, Mre11, Nbs1), in mediating (BRCA1) or transducing (Chk2) the signal, are essential for maintaining genome stability. Notably, mutations in genes encoding these proteins lead to increased risk for cancer.

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Authors
  1. Aude Duprè PhD
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  2. Jean Gautier PhD
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

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Duprè, A., Gautier, J. (2007). Overview of the DNA Damage Checkpoint. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_11

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  • DOI: https://doi.org/10.1007/978-1-59745-221-2_11

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