Safeguarding genetic information is essential to prevent malignant transformation. Two critical cellular processes maintain it free from errors: DNA replication and DNA repair. Importantly, genetic information can be damaged or lost when these processes do not function correctly, ultimately leading to disease. Deregulation and malfunction of the protein machinery that safeguards our genome are hallmarks of cancer, yet it remains unclear how this occurs 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 we can act to correct it and prevent it from happening.
These macromolecules are like real-life machines, equipped with intricate mechanisms that enable them to carry out their activities. We use cryo-electron microscopy and biochemistry in an integrative approach to understand how they operate. Beyond fundamental research, this structural information delivers the necessary details for drug development.
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. Open Access
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