Safeguarding genetic information is essential to avoid malignant transformation. Two key cellular processes keep it free from errors: DNA replication and DNA repair. Importantly, when these do not work correctly, genetic information may be damaged or lost, ultimately leading to disease. Deregulation and malfunction of the protein machinery that safeguards our genome are all hallmarks of cancer, but it remains unclear how this happens at the molecular level. The devil is in the detail, and we aim to understand what goes wrong with these molecular machines and when, so that we can act on it, correct it, and prevent it from happening.
These macromolecules are like real-life machines, with intricate mechanisms that allow them to perform their activities. To understand how they work, we use cryo-electron microscopy (cryo-EM) and biochemistry in an integrative approach. Beyond fundamental research, this structural information provides the necessary detail for drug development.