In-vivo assessment of DNA ligation efficiency and fidelity in cells from patients with Fanconi's anemia and other cancer-prone hereditary disorders

Toxicol Lett. 1993 Apr;67(1-3):309-24. doi: 10.1016/0378-4274(93)90064-5.


We developed a host cell DNA ligation assay, in which we transfected linearized plasmid pZ189 into human lymphoblasts or fibroblasts in order to assess the efficiency and accuracy of DNA ligation within these host cells. We used cell lines from patients with Fanconi's anemia and other chromosome breakage or instability syndromes (Bloom's syndrome, ataxia telangiectasia, Werner's syndrome). With the Fanconi's anemia lymphoblast line GM8010 we did not find a reduced, but a slightly hypermutable DNA ligation. Mutation analysis revealed a unique 7.9-12.5-fold increase in insertions or complex mutations. With cells from the other chromosome breakage/instability syndromes we also found a hypermutable and/or reduced DNA ligation. An impaired DNA ligation might be a common molecular mechanism of genetic instability in these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Transformed
  • DNA / metabolism*
  • DNA Mutational Analysis
  • Fanconi Anemia / genetics*
  • Fibroblasts
  • Genetic Predisposition to Disease
  • Genetic Vectors
  • Humans
  • Lymphocytes
  • Neoplasms / genetics*
  • Plasmids
  • Transfection


  • DNA