Safeguarding genetic information is essential to prevent malignant transformation. Two key cellular processes ensure genome stability: DNA replication and DNA repair. When these systems fail, genetic information can be damaged or lost, ultimately leading to disease. Deregulation and malfunction of the protein machinery that safeguards our genome are, therefore, hallmarks of cancer, yet the molecular mechanisms by which this occurs remain poorly understood.
Our Group investigates the molecular machines that maintain genome integrity, revealing when and how they malfunction in cancer. We use an integrative approach combining cryo-electron microscopy (cryo-EM), biochemistry, and AI-driven protein design technologies. This structural and mechanistic knowledge not only expands our understanding of fundamental biology but also provides the detailed blueprints needed to guide the development of next-generation cancer therapies.
Recent publications
López de Alba E, Salguero I, Giménez-Llorente D, Fernández-Sanromán Á, Casajús-Pelegay E, Terrón-Bautista J, Barroso-González J, Bernal JA, Macintyre G, Fernández-Leiro R, Losada A, Cortés-Ledesma F (2025).A comprehensive genetic catalog of human double-strand break repair. Science 390, eadr5048. CNIO Publication.
Fernandez-Leiro R, Bhairosing-Kok D, Kunetsky V, Laffeber C, Winterwerp HH, Groothuizen F, Fish A, Lebbink JHG, Friedhoff P, Sixma TK, Lamers MH (2021).The selection process of licensing a DNA mismatch for repair.. Nat Struct Mol Biol 28, 373-381. CNIO Publication.
Gutmann C, Takov K, Burnap SA, Singh B, Ali H, Theofilatos K, Reed E, Hasman M, Nabeebaccus A, Fish M, McPhail MJ, O'Gallagher K, Schmidt LE, Cassel C, Rienks M, Yin X, Auzinger G, Napoli S, Mujib SF, Trovato F, Sanderson B, Merrick B, Niazi U, Saqi M, Dimitrakopoulou K, Fernández-Leiro R, Braun S, Kronstein-Wiedemann R, Doores KJ, Edgeworth JD, Shah AM, Bornstein SR, Tonn T, Hayday AC, Giacca M, Shankar-Hari M, Mayr M. (2021).SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care. Nat Commun 12, 3406. CNIO Publication. Open Access
Open Access