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Nucleic Acids Research, 1988, Vol. 16, No. 9 3919-3929
© 1988

Articles

Reduced DNA topoisomerase II activity in ataxia-telangiectasia cells

S.Pal Singh, R. Mohamed1, C. Salmond and M.F. Lavin

Department of Biochemistry, University of Queensland St Lucia, 4067 Brisbane, Queensland, Australia 1Department of Biochemistry, Faculty of Science, UKM Banji 43600 Selangor, Malaysia

Received December 29, 1987. Revised February 17, 1988. Accepted February 17, 1988.

Considerable evidence supports a defect at the level of chromatin structure or recognition of that structure in cells from patients with the human genetic disorder ataxia-telangiectasia. Accordingly, we have investigated the activities of enzymes that alter the topology of DNA in Epstein Barr Virus-transformed lymphoblastoid cells from patients with this syndrome. Reduced activity of DNA topoisomerase II, determined by unknotting of P4 phage DNA, was observed in partially purified extracts from 5 ataxia-telangiectasia cell lines. The level of enzyme activity was reduced substantially in 4 of these cell lines and to a lesser extent in the other cell line compared to controls. DNA topoisomerase I, assayed by relaxation of supercoiled DNA, was found to be present at comparable levels in both cell types. Reduced activity of topoisomerase II in ataxia-telangiectasia is compatible with the molecular, cellular and clinical changes described in this syndrome.


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