We are thrilled to share that the David Lab has been featured in a recent UC Davis Chemistry Department Spotlight! The article, titled “DNA Repair Enzymes: To have an Fe-S cluster or not?”, highlights our ongoing research into the intricate roles that Fe-S clusters—cofactors typically found in redox enzymes—play in DNA repair mechanisms.
The spotlight showcases two of our lab’s recent breakthrough publications:
- Uncovering the Molecular Basis of MUTYH Dysfunction: In a recent Nature Communications paper, we performed structural and functional profiling of inherited cancer-associated variants (CAVs) near the [4Fe-4S] cluster cofactor of the human DNA repair enzyme MUTYH. We discovered a critical allosteric network connecting DNA binding at the cofactor to damaged base removal at the active site. Our findings demonstrate that CAVs disrupt this network to thwart catalysis, providing a clear molecular basis for CAV dysfunction and offering new hypotheses on how oxidative stress impacts DNA repair.
- Adapting to the Absence of a Cofactor: In collaboration with the Fisher Lab, we recently published a paper in Nucleic Acids Research detailing the structure and activity of “MutYX,” a rare “Fe-S clusterless” MutY from the anaerobic bacteria Eggerthella Sp. The structural findings reveal how this enzyme adapted to the absence of the highly conserved cofactor to maintain its DNA repair activity. Because it utilizes completely novel modes of DNA damage recognition, MutYX presents exciting new avenues for development as a biotechnology tool.
A huge congratulations to all our lab members and collaborators who contributed to these exciting discoveries!
Read the full spotlight on the UC Davis Chemistry News Page.
Read our recent publications here:
Nature Communications: https://doi.org/10.1038/s41467-025-58361-w
Nucleic Acids Research: https://doi.org/10.1093/nar/gkaf1127