Role of human Ku86 in telomere length maintenance and telomere capping.
The role of Ku86 at telomeres has been extensively studied in various organisms; however, a role for Ku86 at human telomeres was unknown because Ku86 deletion is lethal for human cells. Here, we used small interference RNA to decrease Ku86 protein levels in human cells. An approximately 50% reduction in the amount of Ku86 protein was achieved 72 hours after transfection with Ku86-specific small interference RNAs. This decrease in Ku86 levels resulted in a rapid loss of cell viability characterized by increased apoptosis and decreased mitotic index in the cell population. Importantly, Ku86 knockdown was concomitant with a significant loss of telomeric sequences and with increased chromosomal aberrations, including chromatid-type fusions involving telomeric sequences. These findings demonstrate a role for Ku86 in regulating telomere length and telomere capping in human cells, which, in turn, could impact on cancer and aging.
Jaco
Isabel
I
Molecular Oncology Program, Spanish National Cancer Center (CNIO), Madrid, Spain.
Muñoz
Purificación
P
Blasco
María A
MA
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002842:Chromatids / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D019098:Telomerase; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen