Show Notes
Cherdyntseva V et al., Nat Commun - 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. Key terms: Lamin A/C, replication fork, H3K9me3, PARylation, RECQ1.
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.
Article title:
Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels
First author:
Cherdyntseva V
Journal:
Nat Commun
DOI:
10.1038/s41467-025-66098-9
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:
CC BY 4.0 / Creative Commons Attribution 4.0 International License
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/nucleoplasmic-lamin-fork-restart
QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-18.
QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript’s substantive coverage of the Lamin A/C–H3K9me3–PAR axis controlling fork slowdown and RECQ1 restart under mild replication stress, including roles of LAP2α, G9a, KDM3A, and ChromStretch mapping.
- transcript topics: Lamin A/C dynamic interaction with replication factories; Acute Lamin A/C depletion and LAP2α effect on fork slowing; RECQ1-mediated fork restart and genetic rescue by RECQ1 depletion; Local PARylation at replication forks and Lamin A/C control; H3K9me3 accumulation at forks and maintenance by Lamin A/C via KDM3A; G9a-driven chromatin methylation and chromatin compaction
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:
- Lamin A/C dynamically interacts with replication factories throughout the nucleus
- Acute Lamin A/C depletion abolishes active fork slowing under mild replication stress; LAP2α depletion yields a similar phenotype
- RECQ1 restart contributes to fork restart; RECQ1 depletion rescues slowed forks
- PARylation levels at replication forks are locally reduced after Lamin A/C loss and can be restored by PARG inhibition
- H3K9me3 accumulates at replication forks under mild replication stress and Lamin A/C maintains this mark by inhibiting the demethylase JMJD1A/KDM3A
- G9a inhibition phenocopies Lamin A/C loss, reducing PAR at forks and deregulating RECQ1 restart; PARG inhibition can rescue
QC result: Pass.
