ANKLE1 processes chromatin bridges by cleaving mechanically stressed DNA

Abstract

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.