Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang.
Ku86 together with Ku70, DNA-PKcs, XRCC4 and DNA ligase IV forms a complex involved in repairing DNA double-strand breaks (DSB) in mammals. Yeast Ku has an essential role at the telomere; in particular, Ku deficiency leads to telomere shortening, loss of telomere clustering, loss of telomeric silencing and deregulation of the telomeric G-overhang. In mammals, Ku proteins associate to telomeric repeats; however, the possible role of Ku in regulating telomere length has not yet been addressed. We have measured telomere length in different cell types from wild-type and Ku86-deficient mice. In contrast to yeast, Ku86 deficiency does not result in telomere shortening or deregulation of the G-strand overhang. Interestingly, Ku86-/- cells show telomeric fusions with long telomeres (>81 kb) at the fusion point. These results indicate that mammalian Ku86 plays a fundamental role at the telomere by preventing telomeric fusions independently of the length of TTAGGG repeats and the integrity of the G-strand overhang.
Samper
E
E
Department of Immunology and Oncology, Centro National de Biotecnología, Spain.
Goytisolo
F A
FA
Slijepcevic
P
P
van Buul
P P
PP
Blasco
M A
MA
D000818:Animals; D034961:Antigens, Nuclear; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D017353:Gene Deletion; D005854:Germ Cells; D017404:In Situ Hybridization, Fluorescence; D000072200:Ku Autoantigen; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C081647:high affinity DNA-binding factor, S cerevisiae; D019098:Telomerase; D015719:Single-Strand Specific DNA and RNA Endonucleases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen