Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction
Abstract Condensin I and topoisomerase IIα (topo IIα) are chromosomal ATPases essential for mitotic chromosome assembly. Mechanistically how the two ATPases cooperate to assemble mitotic chromosomes remains unknown. Here we investigate the interplay between condensin I and topo IIα at single-molecul...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62600-5 |
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| author | Yuko Tsubota Keishi Shintomi Kazuhisa Kinoshita Yuki Masahara-Negishi Yuuki Aizawa Masami Shima Tatsuya Hirano Tomoko Nishiyama |
| author_facet | Yuko Tsubota Keishi Shintomi Kazuhisa Kinoshita Yuki Masahara-Negishi Yuuki Aizawa Masami Shima Tatsuya Hirano Tomoko Nishiyama |
| author_sort | Yuko Tsubota |
| collection | DOAJ |
| description | Abstract Condensin I and topoisomerase IIα (topo IIα) are chromosomal ATPases essential for mitotic chromosome assembly. Mechanistically how the two ATPases cooperate to assemble mitotic chromosomes remains unknown. Here we investigate the interplay between condensin I and topo IIα at single-molecule resolution. While condensin I alone exhibits ATP-dependent DNA loop formation, it generates stable, compact structures (“lumps”) in the presence of topo IIα in a manner dependent on its C-terminal domain. These lumps predominantly contain a single condensin I complex and a single topo IIα dimer. The strand passage activity of topo IIα introduces DNA knots within the lumps, rendering them resistant to protease treatment. An ATP hydrolysis-deficient mutant of condensin I forms smaller lumps, in which the probability of DNA knotting is markedly reduced. Our findings demonstrate that topo IIα-mediated strand passage is functionally coupled with condensin I-mediated loop extrusion, providing insights into the mechanism underlying mitotic chromosome assembly. |
| format | Article |
| id | doaj-art-7ed53e56a44047b1bde6e7cc54d46f9f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7ed53e56a44047b1bde6e7cc54d46f9f2025-08-20T03:46:09ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-62600-5Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compactionYuko Tsubota0Keishi Shintomi1Kazuhisa Kinoshita2Yuki Masahara-Negishi3Yuuki Aizawa4Masami Shima5Tatsuya Hirano6Tomoko Nishiyama7Genome Integrity and Control Laboratory, Division of Biology, Graduate School of Science, Kyoto University, SakyoChromosome Dynamics Laboratory, RIKENChromosome Dynamics Laboratory, RIKENChromosome Dynamics Laboratory, RIKENChromosome Dynamics Laboratory, RIKENChromosome Dynamics Laboratory, RIKENChromosome Dynamics Laboratory, RIKENGenome Integrity and Control Laboratory, Division of Biology, Graduate School of Science, Kyoto University, SakyoAbstract Condensin I and topoisomerase IIα (topo IIα) are chromosomal ATPases essential for mitotic chromosome assembly. Mechanistically how the two ATPases cooperate to assemble mitotic chromosomes remains unknown. Here we investigate the interplay between condensin I and topo IIα at single-molecule resolution. While condensin I alone exhibits ATP-dependent DNA loop formation, it generates stable, compact structures (“lumps”) in the presence of topo IIα in a manner dependent on its C-terminal domain. These lumps predominantly contain a single condensin I complex and a single topo IIα dimer. The strand passage activity of topo IIα introduces DNA knots within the lumps, rendering them resistant to protease treatment. An ATP hydrolysis-deficient mutant of condensin I forms smaller lumps, in which the probability of DNA knotting is markedly reduced. Our findings demonstrate that topo IIα-mediated strand passage is functionally coupled with condensin I-mediated loop extrusion, providing insights into the mechanism underlying mitotic chromosome assembly.https://doi.org/10.1038/s41467-025-62600-5 |
| spellingShingle | Yuko Tsubota Keishi Shintomi Kazuhisa Kinoshita Yuki Masahara-Negishi Yuuki Aizawa Masami Shima Tatsuya Hirano Tomoko Nishiyama Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction Nature Communications |
| title | Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction |
| title_full | Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction |
| title_fullStr | Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction |
| title_full_unstemmed | Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction |
| title_short | Functional interplay between condensin I and topoisomerase Iiα in single-molecule DNA compaction |
| title_sort | functional interplay between condensin i and topoisomerase iiα in single molecule dna compaction |
| url | https://doi.org/10.1038/s41467-025-62600-5 |
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