Scientists discover a 'Goldilocks' zone for DNA organization, opening new doors for drug development

PolyP and magnesium are involved in many biological processes. Thus, the findings could lead to new methods for tuning cellular responses, which could have impactful applications in translational medicine.

The ensuing study, published in Nature Communications on October 26, 2024, reveals a delicate "Goldilocks" zone—a specific magnesium concentration range—where DNA wraps around polyP-magnesium ion condensates. Similar to a thin eggshell covering a liquid-like interior, this seemingly simple structure may help cells organize and protect their genetic material.

This work began as a collaboration between co-senior authors Associate Professor Lisa Racki, Ph.D., and Professor Ashok Deniz, Ph.D., both in the Department of Integrative Structural and Computational Biology at Scripps Research. Racki had been studying these structures in , while Deniz's next-door lab was exploring the physical chemistry of biomolecular condensates for the past decade. Collaboration, they realized, was the only way to unlock these ancient interactions.

"We knew that DNA was in close proximity to the magnesium-rich polyP condensates in cells, but we were totally surprised by the beautiful spheres of DNA that lit up under the microscope," says Racki.

Cryo-electron tomography shows topologies of different types of DNA on polyP condensates. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-53469-x

DNA (yellow) "shells" on the surface of polyP (blue)-magnesium ion condensates dynamically reorganize during droplet fusion. Credit: Scripps Research

Cryo-electron tomography shows that DNA forms "hairy" filaments (cyan arrows in inset image) on the surface of polyP-magnesium ion condensates. Credit: Scripps Research