Telomere dysfunction in aging and cancer.
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.
Gilley
David
D
Department of Medical and Molecular Genetics, The Indiana University Cancer Center, Indiana University School of Medicine, 975 West Walnut St, IB 242, Indianapolis, IN 46202-5251, USA.
Tanaka
Hiromi
H
Herbert
Brittney-Shea
BS
D000375:Aging / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D016922:Cellular Senescence / Q000187:drug effects; D004249:DNA Damage; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D016615:Telomere / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D034501:Telomere-Binding Proteins