Daunomycin-induced unfolding and aggregation of chromatin.
Using equilibrium dialysis and sedimentation velocity analysis, we have characterized the binding of the anti-tumor drug daunomycin to chicken erythrocyte chromatin before and after depletion of linker histones and to its constitutive DNA under several ionic strengths (5, 25, and 75 mM NaCl). The equilibrium dialysis experiments reveal that the drug binds cooperatively to both the chromatin fractions and to the DNA counterpart within the range of ionic strength used in this study. A significant decrease in the binding affinity was observed at 75 mM NaCl. At any given salt concentration, daunomycin exhibits higher binding affinity for DNA than for linker histone-depleted chromatin or chromatin (in decreasing order). Binding of daunomycin to DNA does not significantly affect the sedimentation coefficient of the molecule. This is in contrast to binding to chromatin and to its linker histone-depleted counterpart. In these instances, preferential binding of the drug to the linker DNA regions induces an unfolding of the chromatin fiber that is followed by aggregation, presumably because of histone-DNA interfiber interactions.
Rabbani
A
A
Institute of Biochemistry and Biophysics, University of Tehran Islamic Republic of Iran.
Iskandar
M
M
Ausió
J
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002645:Chickens; D002843:Chromatin / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D003956:Dialysis; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D009994:Osmolar Concentration; D017510:Protein Folding
D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D006657:Histones; D004247:DNA; D003630:Daunorubicin