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

EMBO Rep. 2000 Sep;1(3):244-52. doi: 10.1093/embo-reports/kvd051.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • Bone Marrow Cells
  • Cells, Cultured
  • Chromosome Aberrations / genetics*
  • 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
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Recombination, Genetic / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Single-Strand Specific DNA and RNA Endonucleases / metabolism
  • Spleen / cytology
  • Telomerase / metabolism
  • Telomere / chemistry
  • Telomere / genetics*
  • Telomere / metabolism*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • high affinity DNA-binding factor, S cerevisiae
  • Telomerase
  • Single-Strand Specific DNA and RNA Endonucleases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc5 protein, mouse
  • Xrcc6 protein, human
  • Xrcc6 protein, mouse
  • Ku Autoantigen