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Publication : Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells.

First Author  d'Adda di Fagagna F Year  2001
Journal  Curr Biol Volume  11
Issue  15 Pages  1192-6
PubMed ID  11516951 Mgi Jnum  J:115412
Mgi Id  MGI:3691549 Doi  10.1016/s0960-9822(01)00328-1
Citation  d'Adda di Fagagna F, et al. (2001) Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells. Curr Biol 11(15):1192-6
abstractText  DNA repair by nonhomologous end-joining (NHEJ) relies on the Ku70:Ku80 heterodimer in species ranging from yeast to man. In Saccharomyces cerevisiae and 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 also demonstrate that inactivation of Ku80 or Ku70 in the mouse yields telomeric shortening in various primary cell types at different developmental stages. 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 combination of compromised telomere stability and defective NHEJ.
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