Manipulating mouse telomeres: models of tumorigenesis and aging.
Telomeres are capping structures at the ends of chromosomes, composed of a repetitive DNA sequence and associated proteins. Both a minimal length of telomeric repeats and telomere-associated binding proteins are necessary for proper telomere function. Functional telomeres are essential for maintaining the integrity and stability of eukaryotic genomes. The capping structure enables cells to distinguish chromosome ends from double strand breaks (DSBs) in the genome. Uncapped chromosome ends are at great risk for degradation, recombination, or chromosome fusion by cellular DNA repair systems. Dysfunctional telomeres have been proposed to contribute to tumorigenesis and some aging phenotypes. The analysis of mice deficient in telomerase activity and other telomere-associated proteins has allowed the roles of dysfunctional telomeres in tumorigenesis and aging to be directly tested. Here we will focus on the analysis of different mouse models disrupted for proteins that are important for telomere functions and discuss known and proposed consequences of telomere dysfunction in tumorigenesis and aging.
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Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
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D000375:Aging / Q000235:genetics*; D000818:Animals; D034961:Antigens, Nuclear; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000172:deficiency; D004195:Disease Models, Animal; D000072200:Ku Autoantigen; D051379:Mice; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D012313:RNA; D019098:Telomerase / Q000172:deficiency / Q000235:genetics; D016615:Telomere; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency
D034961:Antigens, Nuclear; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C422952:telomerase RNA; D012313:RNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen