- Samuel Míguez
- Ana González
- Araceli Grande
Safeguarding the genetic information is essential to all forms of life. Two key cellular processes keep it free from errors: DNA replication and repair. Importantly, when either of these processes don’t work properly genetic information may be damaged or lost. This has deleterious effects, ultimately leading to disease. Deregulation and malfunction of the protein machinery that safeguards our genome are a hallmark of cancer, but it still remains unclear how this happens at the molecular level. “The devil is in the detail”, and our aim is to understand to the highest level of detail exactly what goes wrong with these molecular machines, and when, so that we can act on it to correct it as well as to prevent it from happening.
These macromolecules are like real-life machines with intricate mechanisms that enable them to perform their activities. To understand how they work, we use cryo-electron microscopy and biochemistry in an integrative approach. Beyond fundamental research, this structural information provides the necessary details for drug development.
- Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD.(2018)
J Biol Chem 293, 18903-18913.