Rapid DNA repair keeps genome stable

Repair of double-strand breaks in nuclear DNA provides effective protection against the integration of foreign DNA from chloroplasts

To the point

• DNA repair: Plants repair damaged DNA quickly to protect their genome. This repair provides protection against foreign DNA from chloroplasts.
• Genome stability: Research shows that rapid repair of double-strand breaks is crucial for maintaining genome stability in plants.
• Endosymbiotic gene transfer: Endosymbiotic gene transfer carries risks, as inserted DNA can disrupt essential genes and cause genomic instability.
• Research findings: When certain repair mechanisms were deactivated, the integration of chloroplast DNA increased 20-fold.
• Significance for health: The findings could be relevant for cancer research, as genomic instability is associated with tumor development.

The findings, presented by Enrique Gonzalez-Duran and Ralph Bock from the Max Planck Institute of Molecular Plant Physiology, shed new light on endosymbiotic gene transfer — an ongoing evolutionary process in which genes from organelles such as chloroplasts and mitochondria are relocated into the nuclear genome. While successful gene transfers help the nucleus to better coordinate its function with that of the organelles, they also pose risks: mutations arising by DNA insertion can disrupt essential nuclear genes and provoke harmful rearrangements.

The team of researchers discovered that the repair machinery for double-strand breaks has a key role in controlling the frequency of gene transfer. To investigate how plants control endosymbiotic gene transfer, the team focused on the repair pathways for double-strand breaks — known entry points for organellar DNA. Using genetically engineered tobacco plants and a previously developed screening system for endosymbiotic gene transfer events, the researchers selectively inactivated two different double-strand break repair pathways and monitored over 650,000 seedlings for new endosymbiotic gene transfer events.

The results were striking: disabling either of the two repair pathways led to a dramatic increase in gene transfers from chloroplasts to the nucleus — in some cases up to 20-fold. The researchers propose a new model to explain their results: Under normal conditions, plants rapidly repair double-strand breaks in their nuclear DNA, effectively sealing these vulnerable sites before organellar DNA can enter. In this way, the DNA repair machinery serves as a molecular “gatekeeper”. However, when one repair pathway is defective, the other pathways can compensate to some extent, but repair proceeds more slowly. This delay leaves double-strand breaks exposed for longer, thus creating more opportunities for chloroplast DNA to integrate. The result is a surge in gene transfer events, often accompanied by genome rearrangements and increased instability. “The magnitude of the effect suggests that rapid DNA repair is essential for plants to maintain long-term genome stability,” explains Enrique Gonzalez-Duran, first author of the study.

Implications beyond plants

Although the work was carried out in tobacco plants, the team believes the mechanism uncovered is likely universal across eukaryotes. "These DNA repair pathways are conserved in animals and fungi," says Ralph Bock, director of the institute and co-author. “Our findings could explain similar genome instability mechanisms in other organisms, including humans. Further research is needed to clarify this.”

The research opens new avenues for understanding how organellar DNA contributes to mutations in the nuclear genome. It may even have relevance for human health, and in particular to cancer biology, where mitochondrial DNA insertions and genome instability are known molecular triggers of tumor initiation. “Our discovery provides fundamental insights into genome protection and the risks of gene transfer,” adds Gonzalez-Duran. “It reveals how crucial fast DNA repair is — not just to fix damage, but also to defend the integrity of the genome itself.”