title: The absence of the dna-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang.
abstract: The major pathway in mammalian cells for repairing DNA double-strand breaks (DSB) is via nonhomologous end joining. Five components function in this pathway, of which three (Ku70, Ku80, and the DNA-dependent protein kinase catalytic subunit [DNA-PKcs]) constitute a complex termed DNA-dependent protein kinase (DNA-PK). Mammalian Ku proteins bind to DSB and recruit DNA-PKcs to the break. Interestingly, besides their role in DSB repair, Ku proteins bind to chromosome ends, or telomeres, protecting them from end-to-end fusions. Here we show that DNA-PKcs(-/-) cells display an increased frequency of spontaneous telomeric fusions and anaphase bridges. However, DNA-PKcs deficiency does not result in significant changes in telomere length or in deregulation of the G-strand overhang at the telomeres. Although less severe, this phenotype is reminiscent of the one recently described for Ku86-defective cells. Here we show that, besides DNA repair, a role for DNA-PKcs is to protect telomeres, which in turn are essential for chromosomal stability.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain.
authors.forename: F A
authors.initials: FA
authors.lastname: Goytisolo
authors.forename: E
authors.initials: E
authors.lastname: Samper
authors.forename: S
authors.initials: S
authors.lastname: Edmonson
authors.forename: G E
authors.initials: GE
authors.lastname: Taccioli
authors.forename: M A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D000705:Anaphase; D000818:Animals; D002384:Catalysis; D020134:Catalytic Domain; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D008938:Mitosis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases