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Aberrations of DNA Damage in Checkpoints in Cancer

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Book cover Apoptosis, Cell Signaling, and Human Diseases

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Summary

Mutations in gene products controlling DNA damage checkpoints and repair pathways cause predisposition to a large number of sporadic cancers, hereditary cancer syndromes, and developmental defects. This underscores the vital need for the fidelity of checkpoint control and efficiency for the repair machineries. The checkpoint functions are ensured by multiple, often parallel, pathways and show specificity regarding the nature of the damage, cell-cycle phase, and the subsequent cellular response. The checkpoint control mechanisms also link to other cellular responses such as apoptosis to initiate a death program in the event of unsuccesful repair. It is striking that several checkpoint mutations are associated with developmental abnormalities and cancer syndromes, such as the Nijmegen breakage syndrome and Fanconi anemia, indicating that the maintenance of the genome integrity is essential throughout development. Though several critical DNA maintenance proteins have been identified and their links to tumor progression have been established, alterations of several known checkpoint-associated proteins (e.g., 53BP1, Mdc1, SMC1) in cancer are still undiscovered. Knowledge of the DNA damage checkpoint pathways and pathways sensing the damage and instigating repair will pave the way to improved diagnostics, identification of genetic susceptibility, and, in future, rational therapy of cancer.

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Authors and Affiliations

  1. Hartman Institute and Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

    Marikki Laiho

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  1. Marikki Laiho
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  1. Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX

    Rakesh Srivastava

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© 2007 Humana Press Inc., Totowa, NJ

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Laiho, M. (2007). Aberrations of DNA Damage in Checkpoints in Cancer. In: Srivastava, R. (eds) Apoptosis, Cell Signaling, and Human Diseases. Humana Press. https://doi.org/10.1007/978-1-59745-200-7_5

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