Fanconi anemia cells have a normal gene structure for topoisomerase I

Hum Genet. 1994 May;93(5):583-6. doi: 10.1007/BF00202828.

Abstract

Cells from Fanconi anemia (FA) patients have defective DNA repair and are hypersensitive to DNA crosslinking agents such as mitomycin C (MMC). We examined the possibility that topoisomerase I is involved in the DNA crosslink repair system and is deficient in FA group A cells. FA cells and control cells were exposed to MMC with or without camptothecin (CPT), a topoisomerase I inhibitor. The cells did not show any increased sensitivity to killing by MMC with CPT, suggesting that the topoisomerase I is not involved in MMC-damaged DNA repair. However, FA cells showed increased sensitivity to CPT in comparison to control cells, raising the possibility of altered topoisomerase I in FA cells. Therefore, a mutation analysis was performed on topoisomerase I cDNA from FA cells by using chemical cleavage mismatch scanning and nucleotide sequencing. No mutation was detected from GM1309, a group A FA cell line. A base transition (C to T) at position 241, causing an amino acid change (His to Tyr), was found in GM2061, a FA cell line of unknown complementation group. However, allele-specific oligonucleotide hybridization analysis showed that this is a gene polymorphism. We conclude that FA cells have normal gene structure for topoisomerase I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Camptothecin / pharmacology
  • Cell Line / drug effects
  • Cell Survival / drug effects
  • Cell Transformation, Viral
  • Cells, Cultured
  • DNA / biosynthesis
  • DNA Mutational Analysis
  • DNA Primers
  • DNA Topoisomerases, Type I / genetics*
  • Fanconi Anemia / enzymology*
  • Fanconi Anemia / pathology
  • Humans
  • Mitomycin / pharmacology
  • Molecular Sequence Data
  • Polymerase Chain Reaction

Substances

  • DNA Primers
  • Mitomycin
  • DNA
  • DNA Topoisomerases, Type I
  • Camptothecin