Alessandro Costa

Macromolecular Machines Laboratory

A hallmark of cancer cells is genomic instability, arising from errors in the mechanisms that maintain gene copy number and chromosome ploidy.

Our research aims to understand how macromolecular machines involved in DNA replication function to preserve chromosome integrity.

To address these issues, we employ a combination of single-particle cryo-electron microscopy and biochemistry, to generate mechanistic models that explain the basis of key nucleic acid transactions. For example, we are interested in understanding how replicative helicases collaborate with the polymerases to couple DNA unwinding with DNA synthesis.

By describing the architecture and dynamics of the DNA replication/recombination machinery, we seek to establish a molecular framework that explains how higher eukaryotes respond to DNA damage and how cell proliferation is regulated to avoid tumorigenesis.

Selected publications

Abid Ali F,  Renault L,  Gannon J,  Gahlon HL,  Kotecha A,  Zhou JC,  Rueda D Costa A. Cryo-EM structures of the eukaryotic replicative helicase bound to a translocation substrate. Nat. Commun. 2016:18(7):10708. (Abstract)

Maskell, DP; Renault, L; Serrao, E; Lesbats, P; Matadeen, R; Hare, S; Lindemann, D; Engelman, AN; Costa, A and Cherepanov, P (2015) Structural basis for retroviral integration into nucleosomes. Nature 523, 366-369. (co-corresponding author)  (Abstract

Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C, Ivanova ME, Kilkenny ML, Renault L, Kjaer S, Matak-Vinković D, Labib K, Costa A, Pellegrini L.  A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome. Nature. 2014 May 4. (co-corresponding author) (Abstract)

Costa A, Renault L, Swuec P, Petojevic T, Pesavento J, Ilves I, MacLellan-Gibson K, Fleck RA, Botchan M, Berger JM. DNA binding polarity, dimerization, and ATPase ring remodeling in the Cdc45-MCM-GINS replicative helicase. Elife. 2014. (Abstract)

Zhou JC, Costa A. Preparing to unwind. Elife. 2014 Apr 1;3:e02618. (Abstract)

Costa A, Hood IV, Berger JM. Mechanisms for initiating cellular DNA replication. Annu Rev Biochem. 2013;82:25-54. (Abstract)

Costa A, Ilves I, Tamberg N, Petojevic T, Nogales E, Botchan MR, Berger JM. The Structural basis of MCM2-7 Helicase Activation by GINS and Cdc45. Nat Struct Mol Biol. 2011;18(4):471-7. (Abstract)

Costa A, Onesti S. Structural Biology of MCM Helicases. Crit Rev Biochem Mol Biol. 2009;44(5):326-42. (Abstract)

Costa A, van Duinen G, Medagli B, Chong JP, Sakakibara N, Kelman Z, Nair SK, Patwardhan A, Onesti S. Cryo-Electron Microscopy revelas a novel DNA Binding Site on the MCM Helicase. EMBO J. 2008;27(16):2250-8. (Abstract)

 

Alessandro Costa

Alessandro Costa

alessandro.costa@crick.ac.uk
+44 (0)20 379 61812

  • Qualifications and history
  • 2007 PhD, Imperial College London, UK
  • 2007 Postdoctoral fellow, University of Oxford, UK
  • 2009 EMBO Postdoctoral fellow, University of California Berkeley, USA
  • 2012 Establish lab at the London Research Institute, Cancer Research UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK