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Cited by 372DNA Repair MechanismsNuclear Structure and FunctionGenomics and Chromatin Dynamics

Nuclear F-actin and myosins drive relocalization of heterochromatic breaks

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Caridi, Christopher P., D’Agostino, Carla, Ryu, Taehyun, Zapotoczny, Grzegorz, Delabaere, Laetitia, Li, Xiao, Khodaverdian, Varandt Y., Amaral, Nuno +3 more·2018·Nature
DOI 10.1038/s41586-018-0242-8PMC PMC6051730
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Abstract

Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.

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  • Drosophila WAVE, Scar, and ARP2/3-dependent nuclear actin polymerization and myosin are also critical for heterochromatin repair and stability.

    “Drosophila WAVE, Scar, and ARP2/3-dependent nuclear actin polymerization and myosin are also critical for heterochromatin repair and stability87.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [87]

    The ‘Actin nucleators mediate relocalization of heterochromatic DSBs’ section identifies Wash and Scar as Arp2/3 activators in fly cells, but does not identify WAVE as a separate factor. ‘Nuclear F-actin and myosins promote heterochromatin integrity’ concludes that Arp2/3-dependent nuclear actin polymerization and myosins are critical for heterochromatin repair and stability in Drosophila. (LLM, conf=0.86)

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Authors
Caridi, C. P., D’Agostino, C., Ryu, T., Zapotoczny, G., Delabaere, L., Li, X., Khodaverdian, V. Y., Amaral, N., Lin, E., Rau, A. R., & Chiolo, I.
Affiliations
University of Southern California (US)
Corresponding author
Chiolo, Irene
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2018-06-20
Volume
559
Issue
7712
Pages
54-60
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-018-0242-8
PMC
PMC6051730
OpenAlex
W2808968889
Cited by
372
References
3
Citations by year
2026: 21 · 2025: 40 · 2024: 42 · 2023: 59 · 2022: 37 · 2021: 46 · 2020: 54 · 2019: 53 · 2018: 19
FWCI
15.11
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (P40OD018537, P40OD010949)
  • National Institute of General Medical Sciences (R01GM117376)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
heterochromatin, nuclear actin, Arp2/3 complex, homologous recombination, DNA double-strand break repair, chromatin dynamics, chromosomal rearrangements, Drosophila, mouse cells, ectopic recombination
MeSH terms
Animals, Cell Line, Cell Nucleus, Chromosomal Proteins, Non-Histone, Drosophila melanogaster, Heterochromatin, Actin Cytoskeleton, Movement, Myosins, Molecular Chaperones, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Actin-Related Protein 2-3 Complex, Mice, DNA Breaks, Double-Stranded, Recombinational DNA Repair

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