DNA packaging directly affects how fast DNA is copied in cells

Chromatin as a guide

Every day, our cells divide. Each time they need to copy both their DNA and the structure in which the DNA is packed. This packaging, called chromatin, acts as a guide. It tells the cell how, where and when to 'read' and use the information in the DNA. It is important that both the DNA and its chromatin are copied accurately to ensure young and healthy cells. Problems with this process are often seen in diseases like cancer. "Even though this process keeps us healthy, we still don't fully understand how DNA and chromatin are simultaneously copied," says Francesca Mattiroli, group leader.

A unique slowdown alarm

"We found that the copying of chromatin has a direct effect on the mechanisms that copy DNA itself," explains Mattiroli. She and her team found that this effect happens through an unusual stress response. "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," she says. The slower cycle still allows the cell to divide, but the new cells often struggle to continue to grow, preventing them from dividing again.

"So, these mechanisms, which copy DNA and its packaging, are closely connected to cell growth," Mattiroli says. This discovery paves the way for new studies on these pathways and how DNA packaging can control cell growth. In the future, this knowledge could help to find new treatments for diseases like cancer.

A true team effort

"This project was a real adventure for our biochemical lab," says Mattiroli. "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." The research was truly a team effort, with key contributions from co-first authors Jan Dreyer, Giulia Ricci, Jeroen van den Berg as well as from Vivek Bhardwaj and Janina Funk. "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," adds Mattiroli.