Mutations to Ku reveal differences in human somatic cell lines

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

NHEJ (non-homologous end joining) is the predominant mechanism for repairing DNA double-stranded breaks in human cells. One essential NHEJ factor is the Ku heterodimer, which is composed of Ku70 and Ku86. Here we have generated heterozygous loss-of-function mutations for each of these genes in two different human somatic cell lines, HCT116 and NALM-6, using gene targeting. Previous work had suggested that phenotypic differences might exist between the genes and/or between the cell lines. By providing a side-by-each comparison of the four cell lines, we demonstrate that there are indeed subtle differences between loss-of-function mutations for Ku70 versus Ku86, which is accentuated by whether the mutations were derived in the HCT116 or NALM-6 genetic background. Overall, however, the phenotypes of the four lines are quite similar and they provide a compelling argument for the hypothesis that Ku loss-of-function mutations in human somatic cells result in demonstrable haploinsufficiencies. Collectively, these studies demonstrate the importance of proper biallelic expression of these genes for NHEJ and telomere maintenance and they provide insights into why these genes are uniquely essential for primates.

Original languageEnglish (US)
Pages (from-to)762-774
Number of pages13
JournalDNA Repair
Volume7
Issue number5
DOIs
StatePublished - May 3 2008

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Genes
Cells
Cell Line
Mutation
Joining
Haploinsufficiency
Gene Targeting
Double-Stranded DNA Breaks
Essential Genes
Telomere
Primates
Maintenance
Phenotype
Gene Expression
DNA

Keywords

  • DNA-PK
  • Gene targeting
  • Human somatic cell lines
  • Ku
  • NHEJ
  • Telomeres

Cite this

Mutations to Ku reveal differences in human somatic cell lines. / Fattah, Kazi R.; Ruis, Brian L; Hendrickson, Eric A.

In: DNA Repair, Vol. 7, No. 5, 03.05.2008, p. 762-774.

Research output: Contribution to journalArticle

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