title: Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86.
abstract: Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been implicated in the regulation of telomere length although the effect of Ku86 mutations varies considerably between species. Indeed, telomeres either shorten significantly, shorten slightly, remain unchanged, or lengthen significantly in budding yeast, fission yeast, chicken cells, or plants, respectively, that are null for Ku86 expression. Thus, it has been unclear which model system is most relevant for humans. We demonstrate here that the functional inactivation of even a single allele of Ku86 in human somatic cells results in profound telomere loss, which is accompanied by an increase in chromosomal fusions, translocations, and genomic instability. Together, these experiments demonstrate that Ku86, separate from its role in nonhomologous end joining, performs the additional function in human somatic cells of suppressing genomic instability through the regulation of telomere length.
authors.affiliation: 6-155 Jackson Hall, Department of Biochemistry, Molecular Biology, and Biophysics, 321 Church St. SE, University of Minnesota Medical School, Minneapolis, MN 55355, USA.
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
authors.forename: Goutam
authors.initials: G
authors.lastname: Ghosh
authors.forename: Farjana J
authors.initials: FJ
authors.lastname: Fattah
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Amalia
authors.initials: A
authors.lastname: Dutia
authors.forename: Evgenia
authors.initials: E
authors.lastname: Pak
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hendrickson
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D042822:Genomic Instability / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D000072200:Ku Autoantigen; D016615:Telomere / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen