Abstract
Condensin plays an essential role in genome folding through its active DNA loop extrusion activity. Condensin contains a binding interface between its Ycg1 HEAT-repeat subunit and the Brn1 kleisin, together forming a “safety-belt” DNA-binding groove. This safety-belt architecture traps DNA inside the structural maintenance of chromosomes complex and prevents its dissociation during loop extrusion. The entrapment of DNA within the binding pocket of the complex is crucial for ATPase activity and loop extrusion. However, the molecular mechanism underlying DNA entrapment remains unclear. Here, we employ a multiscale computational approach to understand how DNA modulates yeast condensin’s safety-belt dynamics. Using all-atom simulations combined with AlphaFold3 predictions, we demonstrate that DNA binding stabilizes the Ycg1-Brn1 safety belt. Coarse-grained simulations capture the entire DNA-entrapment process and reveal an active regulatory role for DNA: outside the safety belt, DNA triggers opening, whereas once inside, it promotes closure and stabilizes the complex. Kinetic analyses show that the rate-limiting step in DNA entrapment depends on the tightness of the safety belt. A loose safety belt makes the stable closure of its “latch” and “buckle” components rate-limiting, whereas a tighter safety belt shifts the barrier to initial DNA entry.
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Data availability
All the processed data are presented in the main article and the Supplementary Information. Source data are provided in the Source data file. Necessary files for setting up all-atom and CG MD simulations, as well as the AlphaFold3 predicted structural data generated in this study, are publicly available on Zenodo at https://doi.org/10.5281/zenodo.17637587. Protein sequences used for structure prediction were retrieved from UniProtKB under accession codes Q06680 (Ycg1) [https://www.uniprot.org/uniprotkb/Q06680] and P38170 (Brn1) [https://www.uniprot.org/uniprotkb/P38170]. The DNA sequence used for prediction was derived from Protein Data Bank (PDB) entry 5OQO. Previously published protein structures used in this study are available in the PDB under accession codes 5OQO, 7QFW, and 7Q2Z. Source data are provided with this paper.
Code availability
Scripts and code used in this paper have been deposited in Github under accession https://github.com/JChen901/SafetyBeltDataand a backup of this repository is available via https://doi.org/10.5281/zenodo.17637587.
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Acknowledgements
X.C. thanks Prof. Qianyuan Tang for the useful discussion. X.C. acknowledges support from the National Natural Science Foundation of China (Grant Nos. 12474201 and 32201020), the General Program of the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2024A1515010862), the Guangdong Provincial Project (Grant No. 2023QN10X037) and the Guangdong S&T Program (Grant No. 2025A0505000027). Y.W. thanks the Information Technology Center and State Key Lab of CAD&CG, Zhejiang University, for computational support. The authors also acknowledge the Green e Materials Laboratory (GeM) and HPC+AI Intelligence Computing Center at the Hong Kong University of Science and Technology (Guangzhou) for providing computational support.
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J.C. and X.C. conceived the overall study. J.C. performed and analyzed all simulations under the supervision of X.C. X.C., Y.W., and C.F. participated in discussions during the study and contributed to the development of the methodology. J.C. wrote the first draft of the manuscript with input from X.C. and Y.W. All authors contributed to the writing of the manuscript.
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Chen, J., Feng, C., Wang, Y. et al. DNA actively regulates the “safety-belt” dynamics of condensin during loop extrusion. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68239-6
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DOI: https://doi.org/10.1038/s41467-025-68239-6
