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Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding

Author

Listed:
  • Aditi Kaushik

    (University of Aberdeen)

  • Thane Than

    (University of Sheffield)

  • Naomi J. Petela

    (University of Oxford)

  • Menelaos Voulgaris

    (University of Oxford)

  • Charlotte Percival

    (University of Sheffield)

  • Peter Daniels

    (University of Sheffield)

  • John B. Rafferty

    (University of Sheffield)

  • Kim A. Nasmyth

    (University of Oxford)

  • Bin Hu

    (University of Aberdeen)

Abstract

The ring-shaped cohesin complex is a key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here, using Saccharomyces cerevisiae as a model system, we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3’s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process.

Suggested Citation

  • Aditi Kaushik & Thane Than & Naomi J. Petela & Menelaos Voulgaris & Charlotte Percival & Peter Daniels & John B. Rafferty & Kim A. Nasmyth & Bin Hu, 2023. "Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41596-w
    DOI: 10.1038/s41467-023-41596-w
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    References listed on IDEAS

    as
    1. Yasuto Murayama & Frank Uhlmann, 2014. "Biochemical reconstitution of topological DNA binding by the cohesin ring," Nature, Nature, vol. 505(7483), pages 367-371, January.
    2. Matthew A. Deardorff & Masashige Bando & Ryuichiro Nakato & Erwan Watrin & Takehiko Itoh & Masashi Minamino & Katsuya Saitoh & Makiko Komata & Yuki Katou & Dinah Clark & Kathryn E. Cole & Elfride De B, 2012. "HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle," Nature, Nature, vol. 489(7415), pages 313-317, September.
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