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SRBD1 facilitates chromosome segregation by promoting topoisomerase IIα localization to mitotic chromosomes

Author

Listed:
  • Courtney A. Lovejoy

    (Vanderbilt University School of Medicine)

  • Sarah R. Wessel

    (Vanderbilt University School of Medicine
    BPGbio)

  • Rahul Bhowmick

    (Vanderbilt University School of Medicine)

  • Yuki Hatoyama

    (Mishima
    Mishima)

  • Masato T. Kanemaki

    (Mishima
    Mishima
    The University of Tokyo)

  • Runxiang Zhao

    (Vanderbilt University School of Medicine)

  • David Cortez

    (Vanderbilt University School of Medicine)

Abstract

Accurate sister chromatid segregation requires remodeling chromosome architecture, decatenation, and attachment to the mitotic spindle. Some of these events are initiated during S-phase, but they accelerate and conclude during mitosis. Here we describe SRBD1 as a histone and nucleic acid binding protein that prevents DNA damage in interphase cells, localizes to nascent DNA during replication and the chromosome scaffold in mitosis, and is required for chromosome segregation. SRBD1 inactivation causes micronuclei, chromatin bridges, and cell death. Inactivating SRBD1 immediately prior to mitotic entry causes anaphase failure, with a reduction in topoisomerase IIα localization to mitotic chromosomes and defects in properly condensing and decatenating chromosomes. In contrast, SRBD1 is not required to complete cell division after chromosomes are condensed. Strikingly, depleting condensin II reduces the severity of the anaphase defects in SRBD1-deficient cells by restoring topoisomerase IIα localization. Thus, SRBD1 is an essential genome maintenance protein required for mitotic chromosome organization and segregation.

Suggested Citation

  • Courtney A. Lovejoy & Sarah R. Wessel & Rahul Bhowmick & Yuki Hatoyama & Masato T. Kanemaki & Runxiang Zhao & David Cortez, 2025. "SRBD1 facilitates chromosome segregation by promoting topoisomerase IIα localization to mitotic chromosomes," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56911-w
    DOI: 10.1038/s41467-025-56911-w
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    References listed on IDEAS

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    1. Aisha Yesbolatova & Yuichiro Saito & Naomi Kitamoto & Hatsune Makino-Itou & Rieko Ajima & Risako Nakano & Hirofumi Nakaoka & Kosuke Fukui & Kanae Gamo & Yusuke Tominari & Haruki Takeuchi & Yumiko Saga, 2020. "The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Emily C. Dykhuizen & Diana C. Hargreaves & Erik L. Miller & Kairong Cui & Andrey Korshunov & Marcel Kool & Stefan Pfister & Yoon-Jae Cho & Keji Zhao & Gerald R. Crabtree, 2013. "BAF complexes facilitate decatenation of DNA by topoisomerase IIα," Nature, Nature, vol. 497(7451), pages 624-627, May.
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