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Our DNA is carefully packaged inside the cell nucleus, to control how each cell in our body behaves. When a cell divides, its DNA must first be copied and then re-packaged precisely, so that each new cell receives the correct information. This process is essential for normal development, the maintenance of healthy tissues, and is often disrupted in diseases such as cancer. By understanding how this packaging works, we can uncover new ways to treat disease and prevent ageing.

This thesis investigates how human cells carry out the critical task of packaging copied DNA. We developed human cells in which this process can be quickly turned off, allowing us to study the immediate effects. We found that when packaging is disrupted, the copying of DNA slows down, and the DNA structure becomes unusually loose. Remarkably, even one faulty cell division was enough to make cells stop dividing altogether; a strong protective response to avoid passing on damaged information. We discovered which genes become activated when packaging goes wrong, and what interactions are in place to control DNA packaging. In summary, this work sheds light on how cells sense and respond to DNA packaging errors and reveals new players that help protect genome integrity. Future research will explore how these processes can be targeted to better understand, prevent, or treat diseases linked to faulty DNA packaging.