Telomere dysfunction in aging and cancer

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• 作者：Gilley ; David ; Tanaka ; Hiromi ; Herbert ; Brittney-Shea
• 关键词：hTERT ; human telomerase reverse transcriptase catalytic subunit ; hTR ; human telomerase RNA ; DSB ; double-strand breaks ; TRF1/2 ; telomere repeat binding factor 1/2 ; ALT ; alternative lengthening of telomeres ; DNA-PKcs ; DNA-dependent protein kinase catalytic
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2005
• 出版时间：May, 2005
• 年：2005
• 卷：37
• 期：5
• 页码：1000-1013
• 全文大小：227 K

文摘

Telomeres are unique DNA-protein structures that contain noncoding TTAGGG repeats and telomere-associated proteins. These specialized structures are essential for maintaining genomic integrity. Alterations that lead to the disruption of telomere maintenance result in chromosome end-to-end fusions and/or ends being recognized as double-strand breaks. A large body of evidence suggests that the cell responds to dysfunctional telomeres by undergoing senescence, apoptosis, or genomic instability. In conjunction with other predisposing mechanisms, the genomic instability encountered in preimmortal cells due to dysfunctional or uncapped telomeres might lead to cancer. Furthermore, telomere dysfunction has been proposed to play critical roles in aging as well as cancer progression. Conversely, recent evidence has shown that targeting telomere maintenance mechanisms and inducing telomere dysfunction in cancer cells by inhibiting telomerase can lead to catastrophic events including rapid cell death and increased sensitivity to other cancer therapeutics. Thus, given the major role telomeres play during development, it is important to continue our understanding telomere structure, function and maintenance. Herein, we provide an overview of the emerging knowledge of telomere dysfunction and how it relates to possible links between aging and cancer.