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Department of Biochemistry

 
Luca Pellegrini

Molecular mechanisms of genomic stability.

 

Every time a cell divides it must duplicate its genome accurately and completely. Genetic inheritance relies on DNA replication, the biochemical process that is responsible for the accurate duplication of our genome and for the repair of lesions that might block DNA synthesis or alter the encoded information.

The Pellegrini Group wants to understand at the molecular level how our cells execute the orderly duplication of the genome and how they cope with DNA damage. We aim to achieve our goal by working out the 3D shape of the protein complexes responsible for the duplication process then using this information to explain their mechanism of action in atomic detail.

Elucidating the molecular basis of DNA replication is important because the genomic instability caused by defective replication is a major cause of diseases such as cancer, as well as developmental and neurodegenerative pathologies. Our efforts will advance the molecular understanding of genome biology and our ability to translate such knowledge into medical diagnosis and treatment.

 

Research objectives

  • What are the fundamental mechanisms that control DNA synthesis in human cells?

  • How does the molecular machinery of DNA replication cope with obstacles to DNA synthesis?

  • How does homologous recombination assist in the process of DNA replication?

 

Key publications

Evrin C, Maman JD, Diamante A, Pellegrini L, Labib K (2018). Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin. EMBO J., 37(19):e99021. doi: 10.15252/embj.201899021

Brouwer I, Moschetti T, Candelli A, Garcin EB, Modesti M, Pellegrini L, Wuite GJ, Peterman EJ (2018). Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA. EMBO J., 37(7):e98162. doi: 10.15252/embj.201798162

Wu Y, Villa F, Maman J, Lau YH, Dobnikar L, Simon AC, Labib K, Spring DR, Pellegrini L (2017). Targeting the genome-stability hub Ctf4 by stapled-peptide design. Angew. Chem. Int. Ed. Engl., 56(42):12866-12872. doi: 10.1002/anie.201705611

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 (2014). A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome. Nature, 510(7504):293-297. doi: 10.1038/nature13234

Davies OR, Forment JV, Sun M, Belotserkovskaya R, Coates J, Galanty Y, Demir M, Morton CR, Rzechorzek NJ, Jackson SP, Pellegrini L (2015). CtIP tetramer assembly is required for DNA-end resection and repair. Nat. Struct. Mol. Biol., 22(2):150-157. doi: 10.1038/nsmb.2937

Contact details

Research Group Leader  Luca Pellegrini​

Email  lp212@cam.ac.uk

Location  Sanger Building

Opportunities

The Pellegrini Group is accepting enquiries from prospective interns, undergraduate students, postgraduate students and postdoctoral researchers.