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

The major pathway in mammalian cells for repairing DNA double-strand breaks (DSB) is via nonhomologous end joining. Five components function in this p athway, of which three (Ku70, Ku80, and the DNA-dependent protein kinase ca talytic subunit [DNA-PKcs]) constitute a complex termed DNA-dependent prote in 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 fusi ons. Here we show that DNA-PKcs(-/-) cells display an increased frequency o f spontaneous telomeric fusions and anaphase bridges. However, DNA-PKcs def iciency does not result in significant changes in telomere length or in der egulation of the G-strand overhang at the telomeres, Although less severe, this phenotype is reminiscent of the one recently described for Kus6-defect ive 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.