Abstract—

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.

中文翻译：

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棉酚对核小体结构的影响

摘要-

棉酚是一种具有抗病毒，抗氧化剂，抗微生物，抗疟疾和抗肿瘤特性的高活性化合物。众所周知，棉酚的抗肿瘤作用与遗传毒性有关。但是，尚未研究棉酚与染色质的相互作用。在这项工作中，使用基于Förster共振能量转移的单粒子显微镜方法，发现棉酚浓度为10μM或更高时，会导致组蛋白八聚体上核小体DNA构象的重大结构变化。这些改变影响核糖体DNA的至少35bp，使该区域中核糖体DNA的相邻超螺旋回旋之间的距离增加到9nm或更大，并且是由核糖体DNA的解缠引起的。与核心核小体相比，接头DNA区域的存在会稍微增加核小体对棉酚作用的抗性。在30μM和更高的浓度下，棉酚完全破坏了核小体的结构，从而导致组蛋白与DNA分离。获得的数据表明，在体内观察到的棉酚遗传毒性可能与棉酚对染色质的直接作用有关，从而导致核小体结构的破坏。