232: Lamin A/C steers fork restart via H3K9me3 and PARylation

️Episode 232: Lamin A/C steers fork restart via H3K9me3 and PARylation In this episode of PaperCast Base by Base, we explore Nucleoplasmic Lamin A/C, together with LAP2α, enforces active replication fork slowing during mild replication stress by promoting local H3K9me3 and ADP-ribosylation to restrain RECQ1-mediated restart and protect genome stability Study Highlights:Lamin A/C dynamically associates with replication factories throughout the nucleus and its acute depletion abolishes stress-induced fork slowing and increases chromosomal breakage. Loss of nucleoplasmic Lamin A/C or LAP2α reduces poly-ADP-ribosylation (PAR) at nascent DNA, leading to untimely RECQ1-dependent restart of reversed forks. Mild replication stress induces accumulation of H3K9me3 at replication forks, and Lamin A/C is required to maintain this mark by preventing its removal by the demethylase KDM3A/JMJD1A. Inhibiting G9a to prevent H3K9 methylation phenocopies Lamin A/C loss, reducing PAR at forks and deregulating RECQ1 restart, whereas PARG inhibition or KDM3A downregulation restores PAR levels and fork slowing. Conclusion:Nucleoplasmic Lamin A/C maintains local chromatin compaction and PARylation at replication factories to limit RECQ1 activity, enforce fork slowing under mild stress, and preserve genome stability Music:Enjoy the music based on this article at the end of the episode. Reference:Cherdyntseva V, Paulson J, González-Acosta D, Ubieto-Capella P, Rodrigues M, Aouami M, Adakli S, Gagné J-P, Bakker C, Poirier GG, Taneja N, Lopes M. Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels. Nat Commun. 2025. https://doi.org/10.1038/s41467-025-66098-9 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.

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