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Related Experiment Videos

Alteration in the nucleosome and chromatin structures upon interaction with platinum coordination complexes.

C Houssier, M C Depauw-Gillet, R Hacha

    Biochimica Et Biophysica Acta
    |April 15, 1983
    PubMed
    Summary

    Platinum coordination complexes interact with DNA within nucleosomes, altering DNA structure similarly to DNA-platinum complexes. Cis-bidentate platinum ligands significantly destabilize DNA structure, suggesting potential protein-DNA crosslinking.

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    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Biophysics

    Background:

    • Platinum coordination complexes are used in cancer therapy.
    • Nucleosomes and chromatin are the fundamental units of DNA packaging in eukaryotes.
    • Understanding platinum interactions with chromatin is crucial for cancer drug development.

    Purpose of the Study:

    • To investigate the interaction of platinum coordination complexes with nucleosomes and chromatin.
    • To compare the effects of different platinum ligands on DNA structure within nucleosomes.
    • To explore potential mechanisms of platinum-induced DNA damage in chromatin.

    Main Methods:

    • Ultraviolet absorption spectrophotometry
    • Circular and electric linear dichroism

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  • Thermal denaturation
  • Low binding ratio studies (r < 0.1-0.2)

    • Main Results:

    • Platinum complexes interact with nucleosomes and chromatin similarly to DNA-platinum complexes, indicating shared binding sites.
    • Cis-bidentate platinum ligands (cis-dichlorodiammine, diaminocyclohexane, ethylenediamine platinum(II)) caused greater DNA destabilization in nucleosomes than trans-bidentate or monodentate ligands.
    • A significant decrease in negative electric dichroism suggests profound alterations in DNA arrangement, likely due to superhelical condensation.
    • Differences from previous DNA-only studies suggest possible protein-DNA crosslinking in chromatin.

    Conclusions:

    • Platinum coordination complexes bind to DNA within nucleosomes and chromatin.
    • The structure of DNA within nucleosomes is significantly altered by platinum complexation, particularly by cis-bidentate ligands.
    • Observed alterations suggest DNA condensation and potential protein-DNA crosslinking, which may contribute to the biological effects of platinum compounds.