Unlinking of Supercoiled DNA Catenanes by Type IIA Topoisomerases

• Published in: Biophysical journal 2011-09, Vol.101 (6), p.1403-1411
• Main Author: Vologodskii, Alexander
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - metabolism; Biophysics; computer simulation; Deoxyribonucleic acid; DNA; DNA Topoisomerases, Type II - metabolism; DNA, Superhelical - chemistry; DNA, Superhelical - metabolism; DNA-Binding Proteins - metabolism; enzymatic reactions; Enzymes; Models, Molecular; Nucleic Acid; Nucleic Acid Conformation; Plasmids; Proteins; Simulation; supercoiled DNA
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2011.08.011

It was found recently that DNA catenanes, formed during replication of circular plasmids, become positively (+) supercoiled, and the unlinking of such catenanes by type IIA topoisomerases proceeds much more efficiently than the unlinking of negatively (−) supercoiled catenanes. In an attempt to explain this striking finding we studied, by computer simulation, conformational properties of supercoiled DNA catenanes. Although the simulation showed that conformational properties of (+) and (−) supercoiled replication catenanes are very different, these properties per se do not give any advantage to (+) supercoiled over (−) supercoiled DNA catenanes for unlinking. An advantage became evident, however, when we took into account the established features of the enzymatic reaction catalyzed by the topoisomerases. The enzymes create a sharp DNA bend in the first bound DNA segment and allow for the transport of the second segment only from inside the bend to its outside. We showed that in (−) supercoiled DNA catenanes this protein-bound bent segment becomes nearly inaccessible for segments of the other linked DNA molecule, inhibiting the unlinking.