News | Tiny DNA Junctions Found to Regulate Crossing Over and Protect Chromosome Stability
Every new life begins with precise genetic recombination. When eggs or sperm form, maternal and paternal chromosomes pair and exchange DNA segments through crossing over. At least one recombination event per chromosome pair is needed for fertility and stable chromosome numbers, but too many DNA breaks or exchanges can threaten the genome. How do cells maintain the right balance?
A study led by Dr. João Matos at the Max Perutz Labs addressed this longstanding question. The findings were published in Nature in 2025.
The team found that tiny DNA structures called Holliday junctions are more than intermediate steps in crossing over. They also help maintain the zipper-like synaptonemal complex, which connects paired chromosomes. Stable Holliday junctions signal the cell to stop creating DNA breaks, protecting the genome from damage.
“We hypothesized that Holliday junctions are not passive DNA connections but key elements in building and maintaining the synaptonemal complex, ensuring chromosomes remain paired until crossover sites are ready.”
—Dr. João Matos, research team leader
To test the hypothesis, first author Adrian Henggeler used yeast, whose meiotic mechanisms resemble those of human cells and make it a useful genetic model.
Using a molecular tool developed by the laboratory, Henggeler “froze” millions of yeast cells while Holliday junctions and synaptonemal complexes coexisted but before chromosome exchange. He then precisely removed the DNA junctions and observed the cellular response in real time.
“It was one of our eureka moments,” Henggeler recalled. “As soon as the Holliday junctions were removed, the synaptonemal complex collapsed in real time, exactly as we hypothesized and visible under the microscope.”
Without Holliday junctions, the synaptonemal complex immediately disintegrated, new DNA breaks began forming again, and meiosis was disrupted.
“The study reveals a simple, elegant feedback mechanism,” Matos added. “Once crossover sites and the synaptonemal complex are stably established, the cell ‘knows’ it can stop making breaks and proceed with meiosis.”
The next challenge is to determine whether the same mechanism applies to mammals. If confirmed, it could provide important clues about fertility and genome stability across species and new research directions for fertility disorders or chromosomal disease.
News | Tiny DNA Junctions Found to Regulate Crossing Over and Protect Chromosome Stability
News | Tiny DNA Junctions Found to Regulate Crossing Over and Protect Chromosome Stability
Every new life begins with precise genetic recombination. When eggs or sperm form, maternal and paternal chromosomes pair and exchange DNA segments through crossing over. At least one recombination event per chromosome pair is needed for fertility and stable chromosome numbers, but too many DNA breaks or exchanges can threaten the genome. How do cells maintain the right balance?
A study led by Dr. João Matos at the Max Perutz Labs addressed this longstanding question. The findings were published in Nature in 2025.
The team found that tiny DNA structures called Holliday junctions are more than intermediate steps in crossing over. They also help maintain the zipper-like synaptonemal complex, which connects paired chromosomes. Stable Holliday junctions signal the cell to stop creating DNA breaks, protecting the genome from damage.
“We hypothesized that Holliday junctions are not passive DNA connections but key elements in building and maintaining the synaptonemal complex, ensuring chromosomes remain paired until crossover sites are ready.”
—Dr. João Matos, research team leader
To test the hypothesis, first author Adrian Henggeler used yeast, whose meiotic mechanisms resemble those of human cells and make it a useful genetic model.
Using a molecular tool developed by the laboratory, Henggeler “froze” millions of yeast cells while Holliday junctions and synaptonemal complexes coexisted but before chromosome exchange. He then precisely removed the DNA junctions and observed the cellular response in real time.
“It was one of our eureka moments,” Henggeler recalled. “As soon as the Holliday junctions were removed, the synaptonemal complex collapsed in real time, exactly as we hypothesized and visible under the microscope.”
Without Holliday junctions, the synaptonemal complex immediately disintegrated, new DNA breaks began forming again, and meiosis was disrupted.
“The study reveals a simple, elegant feedback mechanism,” Matos added. “Once crossover sites and the synaptonemal complex are stably established, the cell ‘knows’ it can stop making breaks and proceed with meiosis.”
The next challenge is to determine whether the same mechanism applies to mammals. If confirmed, it could provide important clues about fertility and genome stability across species and new research directions for fertility disorders or chromosomal disease.
Source:
Collected online