Topoisomerase VI is a chirally-selective, preferential DNA decatenase
DNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase; however, robust evidence and a mechanism for its preferential decatenation activity wa...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/67021 |
| _version_ | 1811203327482920960 |
|---|---|
| author | Shannon J McKie Parth Rakesh Desai Yeonee Seol Adam MB Allen Anthony Maxwell Keir C Neuman |
| author_facet | Shannon J McKie Parth Rakesh Desai Yeonee Seol Adam MB Allen Anthony Maxwell Keir C Neuman |
| author_sort | Shannon J McKie |
| collection | DOAJ |
| description | DNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase; however, robust evidence and a mechanism for its preferential decatenation activity was lacking. Using single-molecule magnetic tweezers measurements and supporting ensemble biochemistry, we demonstrate that Methanosarcina mazei topo VI preferentially unlinks, or decatenates DNA crossings, in comparison to relaxing supercoils, through a preference for certain DNA crossing geometries. In addition, topo VI demonstrates a significant increase in ATPase activity, DNA binding and rate of strand passage, with increasing DNA writhe, providing further evidence that topo VI is a DNA crossing sensor. Our study strongly suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90°. |
| first_indexed | 2024-04-12T02:53:55Z |
| format | Article |
| id | doaj.art-7222cdcbfb594d06ba876fd0ecf81c30 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:53:55Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7222cdcbfb594d06ba876fd0ecf81c302022-12-22T03:50:54ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.67021Topoisomerase VI is a chirally-selective, preferential DNA decatenaseShannon J McKie0Parth Rakesh Desai1Yeonee Seol2Adam MB Allen3Anthony Maxwell4https://orcid.org/0000-0002-5756-6430Keir C Neuman5https://orcid.org/0000-0002-0863-5671Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States; Department of Biochemistry and Metabolism, John Innes Centre, Norwich, United KingdomLaboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United StatesDepartment of Biochemistry and Metabolism, John Innes Centre, Norwich, United KingdomDepartment of Biochemistry and Metabolism, John Innes Centre, Norwich, United KingdomLaboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United StatesDNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase; however, robust evidence and a mechanism for its preferential decatenation activity was lacking. Using single-molecule magnetic tweezers measurements and supporting ensemble biochemistry, we demonstrate that Methanosarcina mazei topo VI preferentially unlinks, or decatenates DNA crossings, in comparison to relaxing supercoils, through a preference for certain DNA crossing geometries. In addition, topo VI demonstrates a significant increase in ATPase activity, DNA binding and rate of strand passage, with increasing DNA writhe, providing further evidence that topo VI is a DNA crossing sensor. Our study strongly suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90°.https://elifesciences.org/articles/67021single-moleculemagnetic tweezersmethanosarcina mazeiDNA topologytopoisomerase IIB |
| spellingShingle | Shannon J McKie Parth Rakesh Desai Yeonee Seol Adam MB Allen Anthony Maxwell Keir C Neuman Topoisomerase VI is a chirally-selective, preferential DNA decatenase eLife single-molecule magnetic tweezers methanosarcina mazei DNA topology topoisomerase IIB |
| title | Topoisomerase VI is a chirally-selective, preferential DNA decatenase |
| title_full | Topoisomerase VI is a chirally-selective, preferential DNA decatenase |
| title_fullStr | Topoisomerase VI is a chirally-selective, preferential DNA decatenase |
| title_full_unstemmed | Topoisomerase VI is a chirally-selective, preferential DNA decatenase |
| title_short | Topoisomerase VI is a chirally-selective, preferential DNA decatenase |
| title_sort | topoisomerase vi is a chirally selective preferential dna decatenase |
| topic | single-molecule magnetic tweezers methanosarcina mazei DNA topology topoisomerase IIB |
| url | https://elifesciences.org/articles/67021 |
| work_keys_str_mv | AT shannonjmckie topoisomeraseviisachirallyselectivepreferentialdnadecatenase AT parthrakeshdesai topoisomeraseviisachirallyselectivepreferentialdnadecatenase AT yeoneeseol topoisomeraseviisachirallyselectivepreferentialdnadecatenase AT adammballen topoisomeraseviisachirallyselectivepreferentialdnadecatenase AT anthonymaxwell topoisomeraseviisachirallyselectivepreferentialdnadecatenase AT keircneuman topoisomeraseviisachirallyselectivepreferentialdnadecatenase |