Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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NCAPH Stabilizes GEN1 in Chromatin to Resolve Ultra-Fine DNA Bridges and Maintain Chromosome Stability

  • Kim, Jae Hyeong (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Youn, Yuna (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Hwang, Jin-Hyeok (Department of Internal Medicine, Seoul National University Bundang Hospital)
  • Received : 2022.03.25
  • Accepted : 2022.07.17
  • Published : 2022.11.30
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Abstract

Repairing damaged DNA and removing all physical connections between sister chromosomes is important to ensure proper chromosomal segregation by contributing to chromosomal stability. Here, we show that the depletion of non-SMC condensin I complex subunit H (NCAPH) exacerbates chromosome segregation errors and cytokinesis failure owing to sister-chromatid intertwinement, which is distinct from the ultra-fine DNA bridges induced by DNA inter-strand crosslinks (DNA-ICLs). Importantly, we identified an interaction between NCAPH and GEN1 in the chromatin involving binding at the N-terminus of NCAPH. DNA-ICL activation, using ICL-inducing agents, increased the expression and interaction between NCAPH and GEN1 in the soluble nuclear and chromatin, indicating that the NCAPH-GEN1 interaction participates in repairing DNA damage. Moreover, NCAPH stabilizes GEN1 within chromatin at the G2/M-phase and is associated with DNA-ICL-induced damage repair. Therefore, NCAPH resolves DNA-ICL-induced ultra-fine DNA bridges by stabilizing GEN1 and ensures proper chromosome separation and chromosome structural stability.

Keywords

Acknowledgement

This work was supported by grant No. NRF-2021R1A2C200708811 from the National Research Foundation of Korea (NRF). We would like to thank Editage (www.editage.co.kr) for English language editing.

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