Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage
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, co...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/31724 |
| _version_ | 1818019442832965632 |
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| author | Timothy J Wendorff James M Berger |
| author_facet | Timothy J Wendorff James M Berger |
| author_sort | Timothy J Wendorff |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:52:19Z |
| format | Article |
| id | doaj.art-f692e0d3cc59404f972113f45c7c40a1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:52:19Z |
| publishDate | 2018-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f692e0d3cc59404f972113f45c7c40a12022-12-22T02:05:09ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.31724Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passageTimothy J Wendorff0James M Berger1https://orcid.org/0000-0003-0666-1240Biophysics Graduate Program, University of California, Berkeley, Berkeley, United StatesDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United StatesType 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.https://elifesciences.org/articles/31724ATP-dependent molecular machinesDNA topologytype II topoisomerasesprotein-nucleic acid interactionsprotein allostery |
| spellingShingle | Timothy J Wendorff James M Berger Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage eLife ATP-dependent molecular machines DNA topology type II topoisomerases protein-nucleic acid interactions protein allostery |
| title | Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage |
| title_full | Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage |
| title_fullStr | Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage |
| title_full_unstemmed | Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage |
| title_short | Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage |
| title_sort | topoisomerase vi senses and exploits both dna crossings and bends to facilitate strand passage |
| topic | ATP-dependent molecular machines DNA topology type II topoisomerases protein-nucleic acid interactions protein allostery |
| url | https://elifesciences.org/articles/31724 |
| work_keys_str_mv | AT timothyjwendorff topoisomerasevisensesandexploitsbothdnacrossingsandbendstofacilitatestrandpassage AT jamesmberger topoisomerasevisensesandexploitsbothdnacrossingsandbendstofacilitatestrandpassage |