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Single cohesin molecules generate force by two distinct mechanisms

Author

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  • 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
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    References listed on IDEAS

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    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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Yasuto Murayama & Frank Uhlmann, 2014. "Biochemical reconstitution of topological DNA binding by the cohesin ring," Nature, Nature, vol. 505(7483), pages 367-371, January.
    8. 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.
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