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Cited by 156DNA Repair MechanismsMicrotubule and mitosis dynamicsCellular Mechanics and Interactions

Nuclear F-Actin Counteracts Nuclear Deformation and Promotes Fork Repair during Replication Stress

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Lamm, Noa, Read, Mark N., Nobis, Max, Van Ly, David, Page, Scott G., Masamsetti, V. Pragathi, Timpson, Paul, Biro, Maté +1 more·2020·Nature Cell Biology
DOI 10.1038/s41556-020-00605-6

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Abstract

Filamentous actin (F-actin) provides cells with mechanical support and promotes the mobility of intracellular structures. Although F-actin is traditionally considered to be cytoplasmic, here we reveal that nuclear F-actin participates in the replication stress response. Using live and super-resolution imaging, we find that nuclear F-actin is polymerized in response to replication stress through a pathway regulated by ATR-dependent activation of mTORC1, and nucleation through IQGAP1, WASP and ARP2/3. During replication stress, nuclear F-actin increases the nuclear volume and sphericity to counteract nuclear deformation. Furthermore, F-actin and myosin II promote the mobility of stressed-replication foci to the nuclear periphery through increasingly diffusive motion and directed movements along the nuclear actin filaments. These actin functions promote replication stress repair and suppress chromosome and mitotic abnormalities. Moreover, we find that nuclear F-actin is polymerized in vivo in xenograft tumours after treatment with replication-stress-inducing chemotherapeutic agents, indicating that this pathway has a role in human disease.

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  • Nuclear-derived PIP3 is implicated in DNA repair.

    “This nuclear-derived PIP3 is implicated in critical cellular processes such as DNA repair.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [60]

    The Main Text reports that an ATR–IPMK–mTOR pathway promotes replication fork repair through nuclear F-actin. It does not identify nuclear-derived PIP3 or establish a role for PIP3 in that repair; searches for “PIP3” and “phosphatidylinositol” found no such passage. Page numbers are unavailable in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • IPMK-generated PIP3 facilitates polymerization of nuclear actin, essential for recruitment of ATR and participating in replication stress and DNA repair.

    “Two notable studies by Wang et al. [59] and Lamm et al. [60] elucidated that IPMK-generated PIP3 facilitates the polymerization of nuclear actin, essential for the recruitment of ATR (ataxia telangiectasia and Rad3-related protein) and participating in replication stress and DNA repair processes.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [60]

    The Main Text (page unavailable) identifies an ATR–IPMK–mTOR pathway that regulates nuclear actin polymerization during replication stress and promotes replication fork repair. It does not identify IPMK-generated PIP3 as the mediator or say that nuclear actin polymerization is essential for ATR recruitment; instead, it places ATR upstream of the observed actin response. (LLM, conf=0.88)

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Research works printed but not linked: 31

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Cited by

Sorted by citations

Authors
Lamm, N., Read, M. N., Nobis, M., Van Ly, D., Page, S. G., Masamsetti, V. P., Timpson, P., Biro, M., & Cesare, A. J.
Affiliations
  • The University of Sydney (AU)
  • Garvan Institute of Medical Research (AU)
  • UNSW Sydney (AU)
Corresponding author
Cesare, Anthony J.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2020-11-30
Volume
22
Issue
12
Pages
1460-1470
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/s41556-020-00605-6
OpenAlex
W3109203712
Cited by
156
References
6
Citations by year
2026: 11 · 2025: 31 · 2024: 29 · 2023: 30 · 2022: 20 · 2021: 24 · 2020: 8 · 2019: 3
FWCI
6.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cell Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
Funders
  • University of Sydney
  • Hebrew University Smorgon Foundation Fellowship
  • University of Sydney Centre for Excellence in Advanced Food Enginomics
  • Cancer Institute NSW (11/FRL/5-02)
  • St. Vincent’s Clinic Foundation
  • Australian Post-Graduate Award from the University of Sydney
  • Len Ainsworth and Sutton group
  • European Molecular Biology Laboratory Australia
  • Department of Health | National Health and Medical Research Council (1053195, 1106241, 1104461)
  • Cancer Council NSW (RG 15-12)
  • Philanthropy from Stanford Brown, Inc (Sydney, Australia).
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
replication stress, nuclear deformation, ATR signaling, mTORC1, IQGAP1, wasps, Arp2/3 complex, myosin II, chromosomal instability, mitotic abnormalities, tumor xenografts
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Actins, Animals, Antineoplastic Agents, Cell Line, Cell Nucleus, DNA Repair, DNA Replication, Humans, Actin Cytoskeleton, Neoplasms, Carboplatin, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Xenograft Model Antitumor Assays, Cell Line, Tumor, Polymerization

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