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Advances in DNA Repair in Cancer Therapy pp 229–279Cite as

Telomeres, Telomerase, and DNA Damage Response in Cancer Therapy

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D,volume 72))

Abstract

Faithful genome maintenance is essential to an organism’s growth and survival. To preserve genome fidelity, the DNA Damage Response (DDR) pathway has evolved to coordinate the surveillance and repair of genomic DNA, damaged by normal metabolic or environmental insults [1]. DDR surveillance mechanisms scan for discontinuities and structural changes in the DNA double helix. Upon detection of any damage to the DNA molecule, these surveillance sensors activate signal transduction cascades to amplify the damage signal, and coordinate the arrest of proliferation for proper DNA repair [1–4]. Alternatively, apoptosis may be initiated if repair is not possible. The abrupt termini of linear eukaryotic chromosomes pose specific challenges to DDR surveillance, as these natural ends are indistinguishable from damaged double-stranded DNA. In most eukaryotic organisms with linear chromosomes, phylogenetically conserved nucleoprotein structures, known as telomeres, differentiate chromosome ends from nonspecific DNA breaks [5–7]. Telomeres mask the ends of chromosomes from DDR surveillance sensors and protect the chromosome ends from inappropriate repair by DDR mechanisms [8].

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Acknowledgment

We thank Dragony Fu, Suzanne Lee, and Naresh Thumati for reading this chapter and for their helpful comments. Research in Judy Wong’s laboratory is supported by the Canadian Institutes of Health Research, the Canadian Cancer Society, and the Leukemia and Lymphoma Society of Canada. JMYW is supported by the Canada Research Chair and Michael Smith Foundation of Health Research career development programs.

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  1. Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada

    Raina A. Tamakawa, Helen B. Fleisig & Judy M. Y. Wong

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  3. Judy M. Y. Wong
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Correspondence to Judy M. Y. Wong .

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  1. Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, H3T 1E2, Canada

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    Raquel Aloyz

  3. McGill University, Department of Medicine and Oncology, Faculty of Medicine, 3755 Côte Ste-Catherine Road, Montreal, H3T 1E2, Canada

    Moulay Alaoui-Jamali

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Tamakawa, R.A., Fleisig, H.B., Wong, J.M.Y. (2013). Telomeres, Telomerase, and DNA Damage Response in Cancer Therapy. In: Panasci, L., Aloyz, R., Alaoui-Jamali, M. (eds) Advances in DNA Repair in Cancer Therapy. Cancer Drug Discovery and Development, vol 72. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4741-2_11

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