title: Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres.
abstract: Here we analyze the functional interaction between Ku86 and telomerase at the mammalian telomere by studying mice deficient for both proteins. We show that absence of Ku86 prevents the end-to-end chromosomal fusions that result from critical telomere shortening in telomerase-deficient mice. In addition, Ku86 deficiency rescues the male early germ cell apoptosis triggered by short telomeres in these mice. Together, these findings define a role for Ku86 in mediating chromosomal instability and apoptosis triggered by short telomeres. In addition, we show here that Ku86 deficiency results in telomerase-dependent telomere elongation and in the fusion of random pairs of chromosomes in telomerase-proficient cells, suggesting a model in which Ku86 keeps normal-length telomeres less accessible to telomerase-mediated telomere lengthening and to DNA repair activities.
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain.
authors: Silvia
authors: S
authors: Espejel
authors: Sonia
authors: S
authors: Franco
authors: Sandra
authors: S
authors: Rodríguez-Perales
authors: Simon D
authors: SD
authors: Bouffler
authors: Juan C
authors: JC
authors: Cigudosa
authors: María A
authors: MA
authors: Blasco
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear; D017209:Apoptosis / Q000502:physiology*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D000072200:Ku Autoantigen; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology; D019098:Telomerase / Q000172:deficiency / Q000502:physiology*; D016615:Telomere / Q000378:metabolism / Q000502:physiology*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019098:Telomerase; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen