Влияние госсипола на структуру нуклеосом

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, but interaction of gossypol with chromatin was not investigated. In this work,using microscopy of single particles based on the Forster resonance energy transfer it was found that at 10 M or higher concentration, gossypol 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 gyres of nucleosomal DNA in this region to 9 nm or more, and appear to be associated with uncoiling of nucleosomal DNA. The presence of linker DNA somewhat increases the resistance of nucleosomes to the gossypol action, as compared with core nucleosomes. At a concentration of 30 μM or higher, gossypol completely disrupts the structure of nucleosomes, causing dissociation of core 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 destabilization of the nucleosome structure.