Research

Alfredo De Biasio



Curriculum vitae:
Degree in Chemistry, University of Padua.
2008 PhD in Molecular Genetics and Biotechnology, ICGEB, Trieste, Italy
2008-2009 Postdoctoral Fellow, BIDMC and Harvard Medical School, Boston, USA
2009-2013 Juan de la Cierva Postdoctoral Fellow, CIC bioGUNE, Derio, Spain
2014-2017 Postdoctoral Fellow and AIRC-Marie Curie Fellow, Elettra-Sincrotrone Trieste, Italy
2017-2021 Lecturer, Leicester Institute of Structural and Chemical Biology, University of Leicester, UK
2002-2012 Group Leader, Genome Stability Group, ICGEB, Trieste.
Current positions:
Assistant Professor, BESE Division, King Abdullah University for Science and Technology (KAUST), Saudi Arabia
Honorary Lecturer, Leicester Institute of Structural and Chemical Biology, University of Leicester, UK
Young Distinguished Scientist, Elettra-Sincrotrone Trieste, Italy

Contact details:
Address: BESE Division, King Abdullah University for Science and Technology (KAUST), Saudi Arabia
Emailalfredo.debiasio@gmail.com
Webpage: https://www.kaust.edu.sa/en/study/faculty/alfredo-de-biasio



The genetic information is encoded in long chains of deoxyribonucleic acid (DNA) molecules packaged into chromosomes in the cell nucleus. Before dividing, cells need to accurately duplicate their DNA, to ensure that each daughter cell has an identical copy. Critical players in DNA replication are the so-called DNA clamps, ring-shaped proteins that slide on the DNA double helix and anchor DNA polymerases, the enzymes that replicate DNA, to the genomic template. Beside DNA replication, sliding clamps function in the DNA damage response and the maintenance of genome integrity. Due to their central role in cell proliferation, DNA clamps are an important hallmark of tumours, as well as potential drug targets for anti-cancer therapy.
 
Our aim is to unravel the molecular architecture of eukaryotic DNA replication complexes involving DNA sliding clamps, and to shed light on their inner workings. To tackle these composite, supramolecular assemblies we exploit the power of single-particle Cryo-Electron Microscopy (Cryo-EM).
 
In collaboration with Samir Hamdan’s laboratory at KAUST, we have recently determined the Cryo-EM structure of the human holoenzyme that replicates the DNA lagging strand, which includes DNA polymerase δ, primed DNA, PCNA and flap endonuclease 1 (FEN1). We have also determined the structure of the human Pol κ-PCNA-DNA complex, the holoenzyme that replicates DNA through regions of damage.
Current projects are focused on the working principles of the Simian Virus-40 replisome, which makes use of the viral L-Tag helicase and host replication machinery for viral propagation.


Selected publications (*Corresponding author)

  • Lancey C., Tehseen M., Takahashi M., Sobhy M.A., Ragan T.J., Crehuet R., Hamdan S.M.* and De Biasio A.* “Cryo-EM structure of Pol k-DNA-PCNA holoenzyme and implications for polymerase switching in DNA lesion bypass” Preprint at https://www.biorxiv.org/content/10.1101/2020.07.10.196956v1and in peer review in Nature Communications       
  • Lancey C., Tehseen M., Raducanu V.S., Rashid F., Merino N., Ragan T.J., Savva C., Zaher M.S., Shirbini A., Blanco F.J., Hamdan S.M.* and De Biasio A.* (2020) “Structure of the processive human Pol dholoenzyme”, Nat. Commun. 11: 1109
  • De March M., Barrera-Vilarmau S., Crespan E., Mentegari E., Merino N., Gonzalez-Magaña A., Romano-Moreno M., Maga G., Crehuet R., Onesti S., Blanco F.J. and De Biasio A.* (2018) “p15PAF binding to PCNA modulates the DNA sliding surface” Nucleic Acids Res. 46(18): 9816-9828.
  • De March M., Merino N.,Barrera-Vilarmau S., Crehuet R., Onesti S.*, Blanco F.J.* and De Biasio A.* (2017) “Structural basis of human PCNA sliding on DNA” Nat. Commun. 7, 13935 **  [** this paper was reviewed in Yao N. and O'Donnell M. “DNA Replication: How Does a Sliding Clamp Slide?” (2017) Curr. Biol. 27(5):R174-R176]
  • De Biasio A.*, Ibañez de Opakua A., Mortuza G., Molina A., Cordeiro T.N., Castillo F., Villate M., Merino N.,Delgado S., Gil-Cartón D., Luque I., Diercks T., Bernadó P., Montoya G. and Blanco F.J.* (2015) “Structure of p15PAF‒PCNA complex and implications for clamp sliding during DNA replication and repair” Nat. Commun. 6:6439.
     
Ultima modifica il Venerdì, 21 Ottobre 2022 13:49