Membrane-Repair Proteins Step In to Shield Fragile DNA Bridges During Cell Division

Each time a cell divides, it must copy and distribute its DNA precisely between the two new cells. Sometimes chromosomes fail to fully separate, leaving thin strands of DNA, called DNA bridges, connecting the two new cells. These fragile structures are vulnerable to damage and, left unmanaged, can threaten genome stability.

A team from King’s College London, the University of Utah, and biotechnology company Altos Labs has described how cells guard against this risk. Published in Nature Structural & Molecular Biology, the study shows that ESCRT-III proteins, previously known for reshaping and repairing cell membranes, also protect DNA bridges during division.

The researchers found that a safety mechanism called the NoCut checkpoint delays the final stages of division when DNA bridges are present, giving ESCRT-III proteins time to reach the bridges and coat the exposed DNA to prevent damage. DNA bridges are rare in healthy cells but linked to genome instability and early cancer-associated events; the study doesn’t directly tie the mechanism to cancer, but offers insight into how cells guard against this damage.

Juan Martin-Serrano, co-senior author of the study, said: “The discovery came from an unexpected observation. We saw ESCRT proteins binding to DNA but didn’t understand why. After more than 20 years studying these proteins, I never imagined we would uncover this completely new role for them. There is still much more to understand, and our next steps will be to investigate how these DNA bridges form and what enables them to protect the genome.” 

To study these events molecularly, the team used cryo-electron microscopy to resolve the ESCRT/DNA complex structure and live-cell microscopy with fluorescently labelled proteins to track DNA and ESCRT proteins during division. Because DNA bridges are rare, researchers screened large cell populations for natural bridges and temporarily blocked a DNA-separation protein to generate more for study.

Co-first author James Glover said: “When we think about cell division, we often imagine the textbook picture of one cell dividing into two cells with DNA being perfectly distributed. But in reality, many complications can happen as those cells separate. What we’ve discovered is that ESCRT proteins can come in and protect DNA bridges, preventing them from causing damage. The fact that a family of proteins known for remodeling membranes can also protect DNA is such an unexpected and exciting discovery.”