The Effect of Gossypol on the Structure of Nucleosomes

— Gossypol is a highly active compound with antiviral, antioxidant, antimicrobial, antimalarial, and antitumor properties. It is known that the antitumor effect of gossypol is associated with genotoxicity; however, gossypol interaction with chromatin was not studied. In this work, using the method of single particle microscopy based on the Förster resonant energy transfer, it was found that gossypol at concentrations of 10 μM and higher causes significant structural changes in the conformation of nucleosomal DNA on the histone octamer. These changes affect at least 35 bp of nucleosomal DNA, increase the distance between neighboring superhelical gyres of nucleosomal DNA in this region to 9 nm or more, and are caused by unwrapping of nucleosomal DNA. The presence of linker DNA regions slightly increases the resistance of nucleosomes to the gossypol action compared with core nucleosomes. At the concentration of 30 μM and higher, gossypol completely disrupts the structure of nucleosomes, causing dissociation of histones from DNA. The obtained data indicate that gossypol genotoxicity observed in vivo could be associated with a direct effect of gossypol on chromatin, leading to disruption of the nucleosome structure.