title: Heterozygous inactivation of human Ku70/Ku86 heterodimer does not affect cell growth, double-strand break repair, or genome integrity.
abstract: Ku, the heterodimer of Ku70 and Ku86, plays crucial roles in non-homologous end-joining (NHEJ), a major pathway for repairing DNA double-strand breaks (DSBs) in mammalian cells. It has recently been reported that heterozygous disruption of the human KU86 locus results in haploinsufficient phenotypes, including retarded growth, increased radiosensitivity, elevated p53 levels and shortened telomeres. In this paper, however, we show that heterozygous inactivation of either the KU70 or KU86 gene does not cause any defects in cell proliferation or DSB repair in human somatic cells. Moreover, although these heterozygous cell lines express reduced levels of both Ku70 and Ku86, they appear to maintain overall genome integrity with no elevated p53 levels or telomere shortening. These results clearly indicate that Ku haploinsufficiency is not a commonly observed phenomenon in human cells. Our data also suggest that the impact of KU70/KU86 mutations on telomere metabolism varies between cell types in humans.
authors.affiliation: Kihara Institute for Biological Research, Graduate School of Integrated Science, Yokohama City University, Totsuka-ku, Yokohama 244-0813, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Uegaki
authors.forename: Noritaka
authors.initials: N
authors.lastname: Adachi
authors.forename: Sairei
authors.initials: S
authors.lastname: So
authors.forename: Susumu
authors.initials: S
authors.lastname: Iiizumi
authors.forename: Hideki
authors.initials: H
authors.lastname: Koyama
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics*; D002455:Cell Division; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019281:Dimerization; D020868:Gene Silencing; D018390:Gene Targeting; D042822:Genomic Instability; D045325:HCT116 Cells / Q000473:pathology; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D016615:Telomere / Q000235:genetics
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D004247:DNA; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen