223: Torsion Controls Replication: Stall and Restart

Xiaomeng Jia et al., Berger, Smita S - New single-molecule angular optical trap assays reveal that DNA torsion directly controls T7 replisome stalling and reactivation. Key terms: DNA replication, torsion, replisome, helicase, DNA polymerase. 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. First author:Xiaomeng Jia Journal:Nature Communications DOI:10.1038/s41467-025-65567-5 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 On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/torsion-dna-replication-restart ️ Episode:223: Torsion Regulates DNA Replication Stalling and Restart ️ Season:1 Article title:Torsion is a dynamic regulator of DNA replication stalling and reactivation QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-09. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the substantive scientific content describing torque generation by the T7 replisome, stall under torsion, fork regression, restart mechanisms (including excess DNAP and CTD recruitment), and gyrase effects; cross-checked against the original article.- transcript topics: Torque generation by the T7 replisome (AOT measurements); Stalling of replication under torsion and stall torque values; CTD-mediated helicase–DNAP interaction and fork stability; Fork regression dynamics under torsion; Excess DNAP and DNAP exchange promoting fork restart; Gyrase/topoisomerase role in torque relief and restart QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- WT replisome stalls at ~21.9 ± 4.4 pN·nm (≈22 pN·nm) torque when helicase and DNAP act together- DNAP alone and helicase alone generate minimal positive torsion (DNAP ≈ -1.5 ± 2.4 pN·nm; helicase ≈ 1.2 ± 5.0 pN·nm)- ΔCt helicase (la...