Research highlighted as Breakthrough in Nucleic Acid Research

Researchers from the School of Physics and Astronomy in Edinburgh, University of Strathclyde and Seoul National University in South Korea have discovered a new way in which a protein called “structural maintenance of chromosomes” (SMC) helps to organize DNA inside our cells.

The teams found that SMC proteins have a unique geometric shape, which naturally directs them to form DNA loops in a specific direction and orientation. This geometric constraint may be crucial for arranging genetic material but wasn't fully understood before. By using advanced imaging techniques and computer simulations, they uncovered that the shape and binding of this protein enable it to control DNA loops efficiently, without making too many mistakes.

The paper "Spontaneously Directed Loop Extrusion in SMC complexes Emerges from Broken Detailed Balance and Anisotropic DNA Search” has been selected by NAR editors and reviewers as “Nucleic Acids Research Breakthrough Article” collection which highlights the top 1% most influential papers in the field, as they appear to solve a long-standing problem in their field or provide exceptional new insight and understanding into an area of research that will clearly motivate and guide new research opportunities and directions.

This study offers insights that could apply to many organisms, enhancing our understanding of genome organization. Published in Nucleic Acids Research (NAR). Reviewers and editors at NAR who examined this study stated "This study presents a clear, robust, and convincing case for a novel mechanism of SMC-driven loop extrusion...it is an important contribution to the field" and “By combining AFM measurements and molecular dynamics simulation, this work provides a concrete physical picture, vividly visualizing how loop extrusion dynamics is realized and regulated by the SMC complexes in genome organization.”

SMC proteins have recently been discovered to perform so-called “loop extrusion” but no one understands how they do it so effectively in the crowded and entangled environment of a cell’s nucleus. In this study we provide experimental and computational evidence that SMC structure itself may guide efficient loop extrusion by imposing a geometric constraint on its angular motion. We argue that anisotropy and broken detailed balance are the necessary ingredients to explain SMC efficient loop extrusion in vitro and in vivo.

Reference

Bonato A, Jang JW, Kim DG, Moon KW, Michieletto D, Ryu JK. Spontaneously directed loop extrusion in SMC complexes emerges from broken detailed balance and anisotropic DNA search. Nucleic Acids Res. 2025 Jul 19;53(14):gkaf725. doi: 10.1093/nar/gkaf725. PMID: 40744502; PMCID: PMC12313344.

Reference

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