223: Torsion Regulates DNA Replication Stalling and Restart

️ Episode 223: Torsion Regulates DNA Replication Stalling and Restart In this episode of PaperCast Base by Base, we explore New single-molecule angular optical trap assays reveal that DNA torsion directly controls T7 replisome stalling and reactivation Study Highlights:A high-resolution, label-free angular optical trap (AOT) assay was developed to track T7 replisome-driven DNA rotation and torsional slowing in real time. The combined helicase–DNA polymerase (DNAP) replisome generates ∼22 pN·nm of stall torque, about twice that of E. coli RNA polymerase, while helicase or DNAP alone produce minimal positive torque. Loss of the helicase C‑terminal domain interaction with DNAP increases fork regression under torsion and reduces restart efficiency, and prolonged stalling leads to replisome inactivation. Excess free DNAP at the fork and gyrase-mediated torsional relaxation substantially improve restart after a torsion-induced stall Conclusion:Torsional stress is a central regulator of fork stability and restart, with helicase–DNAP synergy and timely topoisomerase activity determining whether stalled replisomes reactivate Music:Enjoy the music based on this article at the end of the episode. Reference:Xiaomeng Jia, Xiang Gao, Shuming Zhang, James T. Inman, Yifeng Hong, Anupam Singh, Fahad Rashid, James M. Berger, Smita S. Patel & Michelle D. Wang. Torsion is a dynamic regulator of DNA replication stalling and reactivation. Nat Commun. 2025;16:10543. https://doi.org/10.1038/s41467-025-65567-5 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com Castos player https://basebybase.castos.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Keywords: DNA replication, torsion, replisome, helicase, DNA polymerase

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