Effect of gossypol on nucleosome structure
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, but interaction of gossypol with chromatin was not investigated. In this work,using microscopy of single particles based on the Förster 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.
About the Authors
N. V. Malyuchenko
Lomonosov Moscow State University
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty
Leninskie Gory 1–12, Moscow, 119234
D. O. Koshkina
Lomonosov Moscow State University
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty
Leninskie Gory 1–12, Moscow, 119234
A. N. Korovina
Lomonosov Moscow State University
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty
Leninskie Gory 1–12, Moscow, 119234
N. S. Gerasimova
Lomonosov Moscow State University
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty
Leninskie Gory 1–12, Moscow, 119234
M. P. Kirpichnikov
Lomonosov Moscow State University
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty
Leninskie Gory 1–12, Moscow, 119234
V. M. Studitsky
Lomonosov Moscow State University; Fox Chase Cancer Center
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty, Cancer Epigenetics Team
Leninskie Gory 1–12, Moscow, 119234
Cottman Avenue 333, Philadelphia, PA 19111, USA
A. V. Feofanov
Lomonosov Moscow State University; Russian Academy of Sciences
Russian Federation
Russian Federation
Bioengineering Department, Biological Faculty, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Leninskie Gory 1–12, Moscow, 119234
ul. Miklukho-Maklaya 16/10, Moscow, 117997
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Review
For citations:
Malyuchenko N.V., Koshkina D.O., Korovina A.N., Gerasimova N.S., Kirpichnikov M.P., Studitsky V.M., Feofanov A.V. Effect of gossypol on nucleosome structure. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2020;75(3):170-175. (In Russ.)
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