Chromosome Folding’s Role in DNA Repair and Genomic Stability

Chromatin compartmentalization regulates the response to DNA damage

This recent study sheds light on the role of chromosome folding in DNA repair and genome stability. When double-stranded breaks occur in mammalian cells, a process driven by ATM (a protein involved in DNA repair) leads to the creation of a new chromatin compartment called the “D compartment.” This compartment forms through a mechanism known as polymer-polymer phase separation and is enriched with specific DNA repair proteins. Importantly, genes involved in responding to DNA damage are physically located within this compartment, aiding in their activation. However, this chromosome reorganization also increases the risk of genetic translocations, which can be observed in cancer genomes. This research highlights the intricate relationship between chromosome architecture and the DNA damage response, providing insights into genomic instability.

Arnould, C., Rocher, V., Saur, F. et al. Chromatin compartmentalization regulates the response to DNA damage. Nature (2023). https://doi.org/10.1038/s41586-023-06635-y