Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage

• Published in: eLife Vol. 7
• Main Authors: Wendorff, Timothy J, Berger, James M
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 29-03-2018; eLife Sciences Publications, Ltd
• Subjects: Adenosine triphosphatase; ATP-dependent molecular machines; Biochemistry and Chemical Biology; Biophysics; Cell growth; Deoxyribonucleic acid; Dimerization; DNA; DNA topoisomerase (ATP-hydrolysing); DNA topoisomerase VI; DNA topology; Enzymes; Glycerol; Meiosis; protein allostery; protein-nucleic acid interactions; Recombination; Self-association; Structural Biology and Molecular Biophysics; Supercoiling; type II topoisomerases; United States > US; California; DNA topology; ATP-dependent molecular machines; chemical biology; biochemistry; structural biology; type II topoisomerases; molecular biophysics; protein allostery; protein-nucleic acid interactions
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.31724

Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association in turn induces extensive DNA bending, which is needed to support duplex cleavage by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover recognition and ATP binding with strand scission, providing useful insights into the operation of type IIB topoisomerases and related meiotic recombination and GHKL ATPase machineries.