Safeguarding genetic information is essential to avoid malignant transformation. Two key cellular processes keep it free from errors: DNA replication and DNA repair. Importantly, genetic information may be damaged or lost when these processes do not work correctly, ultimately leading to disease. The 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 on it 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. We use cryo-electron microscopy and biochemistry in an integrative approach to understand how they work. Beyond fundamental research, this structural information provides the necessary details for drug development.
Publications
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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
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Open Access