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.
Original language | English |
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Article number | 5929 |
Number of pages | 18 |
Journal | Nature Communications |
Volume | 14 |
Issue number | 1 |
Early online date | 22 Sept 2023 |
DOIs | |
Publication status | Published - 22 Sept 2023 |
Bibliographical note
Funding Information:The authors are grateful to Hu and Nasmyth lab members for useful discussions, A Donaldson and A Lorenz for critical reading of the manuscript. B Hu was supported by BBSRC (BB/S002537) and the Wellcome Trust (202062/Z/16/Z).
Data Availability Statement
The data that support this study are available from the corresponding author upon request. The calibrated ChIP-seq data (raw and analysed) were deposited to GEO under accession code GSE217833. All the other original/analysed data including the modelled structures were deposited to figshare: https://doi.org/10.6084/m9.figshare.22664902.v2. The Cryo-EM strucuter of Scc2/J-cohesin was obtained from EMD (EMD-12880). The Cryo-EM strucuter of Scc2/E-cohesin/DNA was obtained from PDB (6ZZ6). The crystal structure of Smc3-Scc1 was obtained from PDB (4UX3). The crystal structure of Smc1-Scc1 was obtained from PDB ((1W1W). Source data are provided with this paper.Supplementary information:
The online version contains supplementary material available at https://doi.org/10.1038/s41467-023-41596-w.
Keywords
- chromosomes
- DNA metabolism
- Molecular Conformation
- Acetylation
- Adenosine Triphosphate
- Saccharomyces cerevisiae/genetics
- Cell Nucleus
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Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding
Hu, B. (Contributor), ScienceDB, 2023
DOI: 10.57760/sciencedb.07984, https://www.doi.org/10.57760/sciencedb.07984
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