Defective Brca2 influences topoisomerase I activity in mammalian cells

Acta Biochim Pol. 2003;50(1):139-44.


The Chinese hamster cell mutant V-C8 is defective in the Brca2 gene (Kraakman-van der Zwet et al., 2002, Cell Biol.; 22: 669). Here we report that V-C8 cells were 10-fold more sensitive to camptothecin, an inhibitor of topoisomerase I, than the parental V79 cells. The level of the relaxation activity of topoisomerase I in nuclear extracts was also lower (4-fold) in V-C8 than V79 cells, in spite of the fact that the level of the topoisomerase I protein was the same in these cells. The survival of V-C8 cells in the presence of camptothecin, the sensitivity of V-C8 topoisomerase I to camptothecin, and the level of the relaxation activity in V-C8 nuclear extract were almost completely restored by transfection of V-C8 cells with the murine Brca2 gene or by the transfer of human chromosome 13 providing the BRCA2 gene. These results indicate that the observed changes in the topoisomerase I activity in V-C8 are due to the defective function of the Brca2 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA2 Protein / genetics*
  • BRCA2 Protein / metabolism*
  • Camptothecin / pharmacology*
  • Cell Line
  • Cell Survival / drug effects*
  • Chromosomes, Human, Pair 13
  • Cricetinae
  • DNA Topoisomerases, Type I / metabolism*
  • Humans
  • Kinetics
  • Mice
  • Recombinant Proteins / metabolism
  • Topoisomerase I Inhibitors
  • Transfection


  • BRCA2 Protein
  • Recombinant Proteins
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • Camptothecin