Genome Integrity and Structural Biology Group

Rafael Fernández Group Leader
T +34 917328000 (Ext 3050)
rfleiro@cnio.es

Research Scientists

Maria Dolores Moreno

Post-Doctoral Fellows

Elena Jiménez

Graduate Students

Ester Casajús
Samuel Míguez

Technicians

Elena Blanco
Araceli Grande

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.

Publications

Rivera-Calzada A, Arribas-Bosacoma R, Ruiz-Ramos A, Escudero-Bravo P, Boskovic J, Fernandez-Leiro R, Oliver AW, Pearl LH, Llorca O. (2022). Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.. Nat Commun 13, 7062. CNIO Publication. Open Access
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.
Lafarga V, Sirozh O, Díaz-López I, Galarreta A, Hisaoka M, Zarzuela E, Boskovic J, Jovanovic B, Fernandez-Leiro R, Muñoz J, Stoecklin G, Ventoso I, Fernandez-Capetillo O (2021). Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides. EMBO J 40, e99692. CNIO Publication.
Dodd T, Botto M, Paul F, Fernandez-Leiro R, Lamers MH, Ivanov I (2020). Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path. Nat Commun 11, 5379. CNIO Publication. Open Access
Míguez Amil S, Jiménez-Ortega E , Ramírez-Escudero M, Talens-Perales D, Marín-Navarro J, Julio Polaina J, Sanz-Aparicio J, Fernandez-Leiro R (2020). The cryo-EM Structure of Thermotoga maritima ß-Galactosidase: Quaternary Structure Guides Protein Engineering. ACS Chem Biol 15, 179-188. CNIO Publication.
Garcia-Carpizo V, Ruiz-Llorente S, Sarmentero J, González-Corpas A, Barrero MJ (2019). CREBBP/EP300 Bromodomain Inhibition Affects the Proliferation of AR-Positive Breast Cancer Cell Lines. Mol Cancer Res 13, 720-730. CNIO Publication.
Famelis N, Rivera-Calzada A, Degliesposti G, Wingender M, Mietrach N, Skehel JM, Fernandez-Leiro R, Böttcher B, Schlosser A, Llorca O, Geibel S (2019). Architecture of the mycobacterial type VII secretion system. Nature 576, 321-325. CNIO Publication.
Barrio JD, Liu J, Brady RA , Tan CSJK, Chiodini S , Ricci M , Fernández-Leiro R , Tsai CJ, Vasileiadi P, Michele LD , Lairez D, Toprakcioglu C ,Scherman OA (2019). Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers. J Am Chem Soc 141, 14021-14025. CNIO Publication.
Muñoz-Hernández H, Pal M, Rodríguez CF, Fernandez-Leiro R, Prodromou C, Pearl LH, Llorca O (2019). Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM. Sci Adv 5, eaaw1616. CNIO Publication. Open Access
Flydal MI, Alcorlo-Pagés M, Johannessen FG, Martínez-Caballero S, Skjærven L, Fernandez-Leiro R, Martinez A, Hermoso JA (2019). Structure of full-length human phenylalanine hydroxylase in complex with tetrahydrobiopterin. Proc Natl Acad Sci USA 116, 11229-11234. CNIO Publication.