Influence of DNA-binding drugs on chromatin condensation.
We have used transient electric dichroism to study the ability of DNA-binding drugs to affect the folding of chromatin from the 10- to the 30-nm fiber, either by themselves or in conjunction with multivalent cations. Variables considered include the cationic charge of the drug, the comparative influence of intercalation and groove binding as modes of interaction, and the effect of bis-intercalation compared to mono-intercalation. In parallel with our findings with other cations, we observe that a drug must have a charge of 3+ or greater in order to condense chromatin at concentrations substantially lower than the concentration of chromatin, measured in base pairs. Drugs of low charge, whether groove binders or mono-or bis-intercalators, are unable to condense chromatin on their own. Bis-intercalators of high charge, however, are extremely efficient condensers, being able to cross-link chromatin with greater efficiency than polyamines of corresponding charge. When Mg2+ is used in combination with bis-intercalators of high charge, the order of addition of the two determines whether compaction or cross-linking is favored. Finally, the antibiotics actinomycin D, daunomycin, and distamycin, despite varied modes of binding to DNA, all inhibit the compaction of chromatin beyond a critical point in a remarkably similar manner.
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D000818:Animals; D002413:Cations, Divalent; D002645:Chickens; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure*; D004247:DNA / Q000097:blood*; D003609:Dactinomycin / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology*; D004214:Distamycins / Q000494:pharmacology; D004563:Electrochemistry; D004912:Erythrocytes / Q000648:ultrastructure; D004996:Ethidium / Q000031:analogs & derivatives / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007364:Intercalating Agents / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D012343:RNA, Transfer / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods
D002413:Cations, Divalent; D002843:Chromatin; D004214:Distamycins; D007364:Intercalating Agents; D003609:Dactinomycin; C037704:bismethidium spermine; D004247:DNA; D012343:RNA, Transfer; D004996:Ethidium; D008274:Magnesium; D003630:Daunorubicin