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Arp2/3 and type-I myosins control chromosome mobility and end-resection at double-strand breaks in S. cerevisiae

Author

Listed:
  • Felix Y. Zhou

    (Brandeis University
    Harvard Medical School)

  • Marissa Ashton

    (Brandeis University)

  • Yiyang Jiang

    (Brandeis University)

  • Neha Arora

    (Brandeis University)

  • Kevin Clark

    (Brandeis University)

  • Kate B. Fitzpatrick

    (Brandeis University)

  • James E. Haber

    (Brandeis University)

Abstract

Using budding yeast, we show that Arp2/3 actin branching complex has an evolutionarily conserved role in promoting chromosome mobility of double-strand breaks (DSBs). The radius of confinement of a broken chromosome is reduced by inhibiting Arp2/3 or by auxin-induced degron depletion of the nucleation promoting factor Las17WASP or type-1 myosins. Arp2/3 and Las17 are required both to initiate and maintain 5’to 3’ resection of DSB ends, whereas depleting Myo3 or Myo5 impairs broken chromosome motion without affecting resection. Conversely, inhibiting Exo1- and Dna2-dependent long-range resection reduces DSB mobility. Inactivating Arp2/3 before DSB induction leads to shortened checkpoint arrest, activating the Tel1ATM/Mre11 (TM) checkpoint. Shortened checkpoint arrest, but not reduced broken chromosome mobility per se, results in reduced interchromosomal homologous recombination. These results suggest that regulating the Arp2/3 complex plays a key role in the processing of DSB ends that is correlated with an increase in DSB mobility and DSB repair.

Suggested Citation

  • Felix Y. Zhou & Marissa Ashton & Yiyang Jiang & Neha Arora & Kevin Clark & Kate B. Fitzpatrick & James E. Haber, 2025. "Arp2/3 and type-I myosins control chromosome mobility and end-resection at double-strand breaks in S. cerevisiae," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62377-7
    DOI: 10.1038/s41467-025-62377-7
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