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Consequences of DNA Intercalation: Protein-Associated DNA Strand Breaks

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Anthracycline Antibiotics in Cancer Therapy

Part of the book series: Developments in Oncology ((DION,volume 10))

Abstract

The intercalation complex of anthracyclines and DNA, previously inferred on the basis of hydrodynamic and optical measurements (1, 2), has recently been given a detailed structural representation by X-ray diffraction analysis (3). A general effect of intercalation is a reduction of winding of the DNA helix. The unwinding angle for daunorubicin (DNR) was estimated from solution studies on superhelical DNA to be ne ar 11°. The X-ray diffraction structure of Quigley et al. (3) yielded a value of 8°, which is in reasonable agreement with the solution studies, but much less than the value of 26° for simple intercalators such as ethidium. A surprising feature of the X-ray structure was that the unwinding by DNR does not occur between the base pairs immediately on either side of the intercalator, but rather is associated with the base pairs one removed from the intercalator. The unwinding effect of intercalation in DNA in intact cells would be expected to distort chromatin structure and could bring into play the action of topoisomerase enzymes which could relieve the distortion.

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© 1982 Martinus Nijhoff Publishers, The Hague

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Kohn, K.W., Zwelling, L.A. (1982). Consequences of DNA Intercalation: Protein-Associated DNA Strand Breaks. In: Muggia, F.M., Young, C.W., Carter, S.K. (eds) Anthracycline Antibiotics in Cancer Therapy. Developments in Oncology, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-7630-6_7

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  • DOI: https://doi.org/10.1007/978-94-009-7630-6_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-009-7632-0

  • Online ISBN: 978-94-009-7630-6

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