IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39696-8.html
   My bibliography  Save this article

Single cohesin molecules generate force by two distinct mechanisms

Author

Listed:
  • Georgii Pobegalov

    (The Francis Crick Institute
    University College London)

  • Lee-Ya Chu

    (The Francis Crick Institute)

  • Jan-Michael Peters

    (Vienna BioCenter)

  • Maxim I. Molodtsov

    (The Francis Crick Institute
    University College London
    Vienna BioCenter)

Abstract

Spatial organization of DNA is facilitated by cohesin protein complexes that move on DNA and extrude DNA loops. How cohesin works mechanistically as a molecular machine is poorly understood. Here, we measure mechanical forces generated by conformational changes in single cohesin molecules. We show that bending of SMC coiled coils is driven by random thermal fluctuations leading to a ~32 nm head-hinge displacement that resists forces up to 1 pN; ATPase head engagement occurs in a single step of ~10 nm and is driven by an ATP dependent head-head movement, resisting forces up to 15 pN. Our molecular dynamic simulations show that the energy of head engagement can be stored in a mechanically strained conformation of NIPBL and released during disengagement. These findings reveal how single cohesin molecules generate force by two distinct mechanisms. We present a model, which proposes how this ability may power different aspects of cohesin-DNA interaction.

Suggested Citation

  • Georgii Pobegalov & Lee-Ya Chu & Jan-Michael Peters & Maxim I. Molodtsov, 2023. "Single cohesin molecules generate force by two distinct mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39696-8
    DOI: 10.1038/s41467-023-39696-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39696-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39696-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Suzana Hadjur & Luke M. Williams & Natalie K. Ryan & Bradley S. Cobb & Tom Sexton & Peter Fraser & Amanda G. Fisher & Matthias Merkenschlager, 2009. "Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus," Nature, Nature, vol. 460(7253), pages 410-413, July.
    2. Jesse R. Dixon & Siddarth Selvaraj & Feng Yue & Audrey Kim & Yan Li & Yin Shen & Ming Hu & Jun S. Liu & Bing Ren, 2012. "Topological domains in mammalian genomes identified by analysis of chromatin interactions," Nature, Nature, vol. 485(7398), pages 376-380, May.
    3. Christian H. Haering & Ana-Maria Farcas & Prakash Arumugam & Jean Metson & Kim Nasmyth, 2008. "The cohesin ring concatenates sister DNA molecules," Nature, Nature, vol. 454(7202), pages 297-301, July.
    4. Kerstin S. Wendt & Keisuke Yoshida & Takehiko Itoh & Masashige Bando & Birgit Koch & Erika Schirghuber & Shuichi Tsutsumi & Genta Nagae & Ko Ishihara & Tsuyoshi Mishiro & Kazuhide Yahata & Fumio Imamo, 2008. "Cohesin mediates transcriptional insulation by CCCTC-binding factor," Nature, Nature, vol. 451(7180), pages 796-801, February.
    5. Ryota Takaki & Atreya Dey & Guang Shi & D. Thirumalai, 2021. "Theory and simulations of condensin mediated loop extrusion in DNA," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. Yasuto Murayama & Frank Uhlmann, 2014. "Biochemical reconstitution of topological DNA binding by the cohesin ring," Nature, Nature, vol. 505(7483), pages 367-371, January.
    7. Elphège P. Nora & Bryan R. Lajoie & Edda G. Schulz & Luca Giorgetti & Ikuhiro Okamoto & Nicolas Servant & Tristan Piolot & Nynke L. van Berkum & Johannes Meisig & John Sedat & Joost Gribnau & Emmanuel, 2012. "Spatial partitioning of the regulatory landscape of the X-inactivation centre," Nature, Nature, vol. 485(7398), pages 381-385, May.
    8. Eugene Kim & Jacob Kerssemakers & Indra A. Shaltiel & Christian H. Haering & Cees Dekker, 2020. "DNA-loop extruding condensin complexes can traverse one another," Nature, Nature, vol. 579(7799), pages 438-442, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Julia Minderjahn & Alexander Fischer & Konstantin Maier & Karina Mendes & Margit Nuetzel & Johanna Raithel & Hanna Stanewsky & Ute Ackermann & Robert Månsson & Claudia Gebhard & Michael Rehli, 2022. "Postmitotic differentiation of human monocytes requires cohesin-structured chromatin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Louisa Hill & Gordana Wutz & Markus Jaritz & Hiromi Tagoh & Lesly Calderón & Jan-Michael Peters & Anton Goloborodko & Meinrad Busslinger, 2023. "Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Shuai Liu & Yaqiang Cao & Kairong Cui & Qingsong Tang & Keji Zhao, 2022. "Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Yi Li & James Lee & Lu Bai, 2024. "DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Alon Diament & Tamir Tuller, 2015. "Improving 3D Genome Reconstructions Using Orthologous and Functional Constraints," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-22, May.
    8. Sonali Narang & Yohana Ghebrechristos & Nikki A. Evensen & Nina Murrell & Sylwia Jasinski & Talia H. Ostrow & David T. Teachey & Elizabeth A. Raetz & Timothee Lionnet & Matthew Witkowski & Iannis Aifa, 2024. "Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Da Lin & Weize Xu & Ping Hong & Chengchao Wu & Zhihui Zhang & Siheng Zhang & Lingyu Xing & Bing Yang & Wei Zhou & Qin Xiao & Jinyue Wang & Cong Wang & Yu He & Xi Chen & Xiaojian Cao & Jiangwei Man & A, 2022. "Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    10. Ryuichiro Nakato & Toyonori Sakata & Jiankang Wang & Luis Augusto Eijy Nagai & Yuya Nagaoka & Gina Miku Oba & Masashige Bando & Katsuhiko Shirahige, 2023. "Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Khalid H. Bhat & Saurabh Priyadarshi & Sarah Naiyer & Xinyan Qu & Hammad Farooq & Eden Kleiman & Jeffery Xu & Xue Lei & Jose F. Cantillo & Robert Wuerffel & Nicole Baumgarth & Jie Liang & Ann J. Feene, 2023. "An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Wu Zuo & Guangming Chen & Zhimei Gao & Shuai Li & Yanyan Chen & Chenhui Huang & Juan Chen & Zhengjun Chen & Ming Lei & Qian Bian, 2021. "Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    13. Li-Hsin Chang & Sourav Ghosh & Andrea Papale & Jennifer M. Luppino & Mélanie Miranda & Vincent Piras & Jéril Degrouard & Joanne Edouard & Mallory Poncelet & Nathan Lecouvreur & Sébastien Bloyer & Amél, 2023. "Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    14. Jia-Yong Zhong & Longjian Niu & Zhuo-Bin Lin & Xin Bai & Ying Chen & Feng Luo & Chunhui Hou & Chuan-Le Xiao, 2023. "High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Jingxuan Xu & Xiang Xu & Dandan Huang & Yawen Luo & Lin Lin & Xuemei Bai & Yang Zheng & Qian Yang & Yu Cheng & An Huang & Jingyi Shi & Xiaochen Bo & Jin Gu & Hebing Chen, 2024. "A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. Theodore Sakellaropoulos & Catherine Do & Guimei Jiang & Giulia Cova & Peter Meyn & Dacia Dimartino & Sitharam Ramaswami & Adriana Heguy & Aristotelis Tsirigos & Jane A. Skok, 2024. "MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Lina Zheng & Wei Wang, 2022. "Regulation associated modules reflect 3D genome modularity associated with chromatin activity," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    18. Gabrielle A. Dotson & Can Chen & Stephen Lindsly & Anthony Cicalo & Sam Dilworth & Charles Ryan & Sivakumar Jeyarajan & Walter Meixner & Cooper Stansbury & Joshua Pickard & Nicholas Beckloff & Amit Su, 2022. "Deciphering multi-way interactions in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Christopher Chase Bolt & Lucille Lopez-Delisle & Aurélie Hintermann & Bénédicte Mascrez & Antonella Rauseo & Guillaume Andrey & Denis Duboule, 2022. "Context-dependent enhancer function revealed by targeted inter-TAD relocation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Ramya Raviram & Pedro P Rocha & Christian L Müller & Emily R Miraldi & Sana Badri & Yi Fu & Emily Swanzey & Charlotte Proudhon & Valentina Snetkova & Richard Bonneau & Jane A Skok, 2016. "4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments," PLOS Computational Biology, Public Library of Science, vol. 12(3), pages 1-23, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39696-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.