Grupo de Integridad Genómica y Biología Estructural

Rafael Fernández Jefe de Grupo
T +34 917328000 (Ext 3050)
rfleiro@cnio.es

Investigadores

Maria Dolores Moreno

Becarios Pre-Doctorales

Ester Casajús
Samuel Míguez

Técnicos de Laboratorio

Araceli Grande

Safeguarding genetic information is essential to all forms of life. Two key cellular processes keep it free from errors: DNA replication and 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 a hallmark 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 and when something goes wrong with these molecular machines, so that we can act to 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.

Publicaciones

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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO.
Del Caño-Ochoa F, Grande-García A, Reverte-López M, D'Abramo M, Ramón-Maiques S (2018). Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD. J Biol Chem 293, 18903-18913. Publicación CNIO.
Lafarga V, Sirozh O, Diaz-Lopez I, Hisaoka M, Zarzuela E, Boskovic J, Jovanovic B, Fernandez-Leiro R, Munoz J, Stoecklin G, Ventoso I, Fernandez-Capetillo O (2018). DNA and RNA binding mediate the toxicity of arginine-rich peptides encoded by C9ORF72 GGGGCC repeats. bioRxiv (in press). Publicación CNIO.