What is it about?

This study aimed to investigate the key regulatory mechanisms controlling the number and spatial distribution of crossovers (COs) during meiosis. Through a genetic screen, we identified the E3 ubiquitin ligase Ufd2p as a crucial novel regulator. It maintains DNA negative supercoil homeostasis by ubiquitinating and degrading Topoisomerase II (Top2p). Loss of Ufd2p function leads to Top2p accumulation, excessive resolution of negative supercoils, which subsequently enhances crossover interference and ultimately reduces CO frequency. This mechanism is highly conserved from yeast to mammals. Our work reveals a novel pathway through which the ubiquitin-proteasome system precisely controls CO formation by regulating DNA topology, providing important molecular insights into the balance between generating genetic diversity and maintaining genomic stability.

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Why is it important?

Meiotic crossovers are essential for chromosome segregation and genetic diversity. However, the molecular mechanisms governing crossover patterns remain incompletely understood. Our work identifies a previously uncharacterized factor required for crossover regulation and uncovers a ubiquitin-based topological control mechanism shaping meiotic crossover landscapes across eukaryotic species.

Perspectives

This research has enabled us to bring together many outstanding investigators to collectively address a scientific question and has allowed us to rejoice in the scientific discoveries we have made. This work has deepened our understanding of the regulation of meiosis—a conserved and ancient biological process—and serves as an important encouragement in our ultimate quest to comprehend sexual reproduction. We hope that more brilliant scientists will join the exploration of this field and work together to unravel the mysteries of life.

Taicong Tan
Guangzhou Medical University

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This page is a summary of: Ufd2p promotes efficient crossover formation by destabilizing Top2p during meiosis, Proceedings of the National Academy of Sciences, February 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2517398123.
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