Role of Golgi complex in DNA repair control
First described in 1898 by renowned Italian biologist Camillo Golgi, after whom the organelle was later named, the Golgi complex is best known as the cell’s sorting and shipping hub. Proteins, the workhorses of the cell, arrive at the Golgi to be processed, packaged, and sent to their appropriate destinations within the cell.
The Group is interested in how proteins move within the cell and how organelles such as the Golgi are built and maintained. The authors found that a whole network of proteins that repair DNA, normally associated with the nucleus, also reside at the Golgi. “Finding DNA-repair proteins at the Golgi at all was unexpected; this is machinery you expect to see in the nucleus,” said a co-first author of the study.
These proteins belonged to many different DNA-repair pathways, with almost every known pathway being represented. The team wanted to understand what these proteins were doing at the Golgi, and what would happen when the cell’s DNA was actually damaged.
When the team induced different types of DNA damage using chemical agents, the repair proteins did not stay static. For each kind of damage, the proteins needed to fix it were recruited from the Golgi into the nucleus, while the proteins not required for that repair were cleared out of the nucleus and sequestered at the Golgi. This dynamic, damage-specific localisation is the heart of the finding. It suggests the cell uses the Golgi as part of a system for controlling when and where DNA-repair proteins act, a layer of regulation that sits outside the nucleus.
To probe how this control works, the team followed one protein in detail: RAD51C, which plays a key role in homologous recombination, a major pathway for repairing breaks in DNA. Mutations in RAD51C are strongly associated with increased risk for certain cancers such as breast and ovarian cancers. They found that RAD51C was held at the Golgi through its interaction with Giantin, one of a family of large Golgi proteins. When DNA was damaged, RAD51C was released and moved to the nucleus, gathering at the sites where DNA is mended. When the researchers disrupted this arrangement by removing Giantin, RAD51C's normal localisation broke down, and DNA repair was stopped.
"This was a very exciting finding, one of the first of its kind," said another co-first author. "It supports the idea that DNA repair isn't only a nuclear process – it's a global process, coordinated across the cell, with organelles like the Golgi helping to control it. This opens up a lot of new questions about how the cytoplasm and the nucleus influence each other."
RAD51C is only one of more than 300 proteins the team found in both the Golgi and the nucleus, and DNA repair is only one part of what the screen uncovered. The shared proteins span many different cellular pathways, pointing to a connection between the Golgi and the nucleus that is far more extensive than previously appreciated and tying cytoplasmic processes directly to what happens to the genome. It raises the question of whether the Golgi’s other functions are linked to nuclear processes in a similar way.
“The work reframes the Golgi as an active participant in the DNA damage response rather than a bystander, an organelle that stores, releases, and times the deployment of repair factors,” said the senior author of the study. “More striking still, it points to cytoplasmic processes being far more closely linked to DNA repair than we assumed.”
