New Insights into the Role of Chromatin in Cellular Processes

The Mattiroli group's researchers discovered that the speed at which DNA is replicated during cell division can be directly influenced by the way DNA is packaged in cells. They found that the capacity of the cell to divide and proliferate is impacted by signals sent by DNA packaging via an odd channel.

This creates new opportunities to investigate the relationship between DNA copying and packaging. These results, which were published in Molecular Cell, could aid future research into treatments and medicines for diseases including cancer.

Chromatin as a Guide

Human cells divide daily. Every time, they must duplicate both their DNA and the structure that contains it. Chromatin, the name for this packaging, serves as a guide. It instructs the cell on when, where, and how to “read” and utilize the data contained in the DNA. To guarantee young, healthy cells, it is critical that the DNA and its chromatin are precisely replicated. Diseases like cancer frequently exhibit issues with this process.

Even though this process keeps us healthy, we still don’t fully understand how DNA and chromatin are simultaneously copied.”

Francesca Mattiroli, Group Leader, Hubrecht Institute

A Unique Slowdown Alarm

“We found that the copying of chromatin has a direct effect on the mechanisms that copy DNA itself”, explained Mattiroli.

She and her colleagues discovered that this impact is caused by an unusual stress response.

Mattiroli added, “If there is a problem with DNA packaging, the cell quickly senses this issue. But instead of triggering a typical stress response, the cell responds by slowing down its cycle of growth and division, without stopping it completely.”

The cell can still divide with the slower cycle, but the new cells frequently find it difficult to develop and are unable to divide again.

“So, these mechanisms, which copy DNA and its packaging, are closely connected to cell growth”, Mattiroli stated.

This finding opens the door to more research on these pathways and the ways that DNA packaging can regulate cell division. This knowledge could one day aid in the development of new treatments to treat diseases like cancer.

A True Team Effort

Mattiroli noted, “This project was a real adventure for our biochemical lab. Without the collaboration with Alexander van Oudenaarden’s lab and our other collaborators, this work would have not been possible. The technology created by Jeroen van den Berg and Vincent van Batenburg was perfect to address the questions we wanted to answer.”

Vivek Bhardwaj, Janina Funk, and study co-first authors Jan Dreyer, Giulia Ricci, and Jeroen van den Berg all made significant contributions to the research, which was genuinely a team effort.

“I really enjoyed learning all of these new things, thanks to the highly collaborative spirit of the Hubrecht Institute. I look forward to doing more cell-based research in the future”, concluded Mattiroli.