Fanconi anemia cells have a normal gene structure for topoisomerase I

Hiroshi Saito, Markus Grompe, Tina L. Neeley, Petra M. Jakobs, Robb E. Moses

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)583-586
Number of pages4
JournalHuman genetics
Issue number5
StatePublished - May 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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