Fd. Di Fagagna et al., Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells, CURR BIOL, 11(15), 2001, pp. 1192-1196
DNA repair by nonhomologous end-joining (NHEJ) relies on the Ku70:Ku80 hete
rodimer in species ranging from yeast to man. In Saccharomyces cerevisiae a
nd Schizosaccharomyces pombe, Ku also controls telomere functions. Here, we
show that Ku70, Ku80, and DNA-PKcs, with which Ku interacts, associate in
vivo with telomeric DNA in several human cell types, and we show that these
associations are not significantly affected by DNA-damaging agents. We als
o demonstrate that inactivation of Ku80 or Ku70 in the mouse yields telomer
ic shortening in various primary cell types at different developmental stag
es. By contrast, telomere length is not altered in cells impaired in XRCC4
or DNA ligase IV, two other NHEJ components. We also observe higher genomic
instability in Ku-deficient cells than in XRCC4-null cells. This suggests
that chromosomal instability of Ku-deficient cells results from a combinati
on of compromised telomere stability and defective NHEJ.