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2003 | 50 | 1 | 139-144
Article title

Defective Brca2 influences topoisomerase I activity in mammalian cells*.

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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.
Physical description
  • Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland
  • Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland
  • Department of Biochemistry, Medical University of Warsaw, Warszawa, Poland
  • Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Molecular Cell Genetics, The L. Rydygier University of Medical Sciences, Bydgoszcz, Poland
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