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<p>Chromatin bridges experience significant tension due to spindle fiber pulling and cell migration. Uncontrolled breakage of chromatin bridges by actomyosin contractile forces leads to detrimental consequences. The existence of specialized mechanisms that process chromatin bridges to prevent catastrophic rupture remains uncertain. Here, we uncover a unique property of ANKLE1, a midbody-tethered endonuclease implicated in chromatin bridge processing, in sensing and responding to DNA tension and supercoiling during cell division. Using single-molecule analyses, we found that ANKLE1 specifically cuts supercoiled or mechanically stretched DNA. At higher stretching forces, ANKLE1 cleaves both strands of negatively supercoiled DNA, mirroring conditions in which stretched chromatin bridges lose histones to expose negatively supercoiled DNA. These findings show that ANKLE1 acts as a DNA tension sensor that resolves stretched chromatin bridges. Our study highlights the significance of mechanical forces in DNA bridge processing, enhances our understanding of how cells preserve genome integrity during cell division.</p>

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ANKLE1 processes chromatin bridges by cleaving mechanically stressed DNA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月8日

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  • Huadong Jiang,
  • Fei He,
  • Nannan Kong,
  • Jie Long,
  • Yu Ching Poon,
  • Rajvee Shah Punatar,
  • Zhichun Xu,
  • Yuanliang Zhai,
  • Stephen C. West,
  • Artem K. Efremov,
  • Ying Wai Chan

摘要

Chromatin bridges experience significant tension due to spindle fiber pulling and cell migration. Uncontrolled breakage of chromatin bridges by actomyosin contractile forces leads to detrimental consequences. The existence of specialized mechanisms that process chromatin bridges to prevent catastrophic rupture remains uncertain. Here, we uncover a unique property of ANKLE1, a midbody-tethered endonuclease implicated in chromatin bridge processing, in sensing and responding to DNA tension and supercoiling during cell division. Using single-molecule analyses, we found that ANKLE1 specifically cuts supercoiled or mechanically stretched DNA. At higher stretching forces, ANKLE1 cleaves both strands of negatively supercoiled DNA, mirroring conditions in which stretched chromatin bridges lose histones to expose negatively supercoiled DNA. These findings show that ANKLE1 acts as a DNA tension sensor that resolves stretched chromatin bridges. Our study highlights the significance of mechanical forces in DNA bridge processing, enhances our understanding of how cells preserve genome integrity during cell division.