Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang

• Published in: EMBO reports 2000-09, Vol.1 (3), p.244-252
• Main Authors: Samper, Enrique, Goytisolo, Fermín A, Slijepcevic, Predrag, van Buul, Paul P W, Blasco, María A
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Nuclear; Bone Marrow Cells; Cells, Cultured; Chromosome Aberrations - genetics; Deoxyribonucleic acid; Deregulation; DNA; DNA Damage - genetics; DNA Helicases; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fibroblasts; Flow Cytometry; Gene Deletion; Germ Cells; In Situ Hybridization, Fluorescence; Ku Autoantigen; Male; Mammals; Mice; Mice, Knockout; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Recombination, Genetic - genetics; Repetitive Sequences, Nucleic Acid - genetics; Saccharomyces cerevisiae Proteins; Scientific Report; Scientific Reports; Single-Strand Specific DNA and RNA Endonucleases - metabolism; Spleen - cytology; Telomerase - metabolism; Telomere - chemistry; Telomere - genetics; Telomere - metabolism; Yeasts
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1093/embo-reports/kvd051

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.