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Genome maintenance and replication - Dr Luca Pellegrini

Abstract:

The faithful inheritance of genetic information is essential to cellular life. Successful transmission of the genetic material requires the accurate replication of the genome and the repair of any DNA lesion that might block replication or alter the encoded message. Failure of the complex molecular systems that preserve the integrity of our DNA is a major contributing factor in human disease. The object of PhD projects in our laboratory is to understand structure and function of the macromolecular assemblies responsible for the maintenance and replication of our genome. We use the tools of structural biology to recover three-dimensional information of proteins and protein complexes important to DNA replication and repair, and we combine the structural evidence with biochemical, biophysical and computational analysis to reveal molecular mechanisms.

References:

  1. Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L. Mechanism  for priming DNA synthesis by yeast DNA Polymerase α. Elife. 2013 Apr 2;2:e00482.   doi: 10.7554/eLife.00482.
  2. Blackwood JK, Rzechorzek NJ, Abrams AS, Maman JD, Pellegrini L, Robinson NP.  Structural and functional insights into DNA-end processing by the archaeal HerA  helicase-NurA nuclease complex. Nucleic Acids Res. 2012 Apr;40(7):3183-96. doi:  10.1093/nar/gkr1157.  
  3. Klinge S, Hirst J, Maman JD, Krude T, Pellegrini L. An iron-sulfur domain of  the eukaryotic primase is essential for RNA primer synthesis. Nat Struct Mol  Biol. 2007 Sep;14(9):875-7.

Dr Luca Pellegrini

Dr Luca Pellegrini

Reader in Structural Biology

Department of Biochemistry
Tennis Court Road
Cambridge CB2 1GA

Office Phone: 01223 760469

Key Publications

Syrjanen JL, Pellegrini L, Davies OR. A molecular model for the role of SYCP3 in meiotic chromosome organisation. eLife 2014 Jun 20:e02963. doi: 10.7554/eLife.02963. [Epub ahead of print]

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 510 293-7

Kilkenny ML, Longo MA, Perera RL, Pellegrini L. Structures of human primase reveal design of nucleotide elongation site and Pol α tethering. PNAS 2013 110 15961-6.

Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L. Mechanism for priming DNA synthesis by yeast DNA Polymerase α. eLife 2013;2:00482 

Davies OR, Maman JD, Pellegrini L. Structural analysis of the human SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly. Open Biol. 2012 2 120099

Kilkenny ML, De Piccoli G, Perera RL, Labib K, Pellegrini L. A conserved motif in the C-terminal tail of DNA polymerase α tethers primase to the eukaryotic replisome. J Biol Chem. 2012 287 23740-7

Núñez-Ramírez R, Klinge S, Sauguet L, Melero R, Recuero-Checa MA, Kilkenny M, Perera RL, García-Alvarez B, Hall RJ, Nogales E, Pellegrini L, Llorca O. Flexible tethering of primase and DNA Pol α in the eukaryotic primosome. Nucleic Acids Res. 2011 39 8187-99

Blackwood JK, Rzechorzek NJ, Abrams AS, Maman JD, Pellegrini L, Robinson NP. Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex. Nucleic Acids Res. 2012 40 3183-96

Sauguet L, Klinge S, Perera RL, Maman JD, Pellegrini L. Shared active site architecture between the large subunit of eukaryotic primase and DNA photolyase. PLoS One 2010 5 e10083

Klinge S, Núñez-Ramírez R, Llorca O, Pellegrini L. 3D architecture of DNA Pol α reveals the functional core of multi-subunit replicative polymerases. EMBO J. 2009 28 1978-87.

Ragone S, Maman JD, Furnham N, Pellegrini L. Structural basis for inhibition of homologous recombination by the RecX protein. EMBO J. 2008 27 2259-69

Klinge S, Hirst J, Maman JD, Krude T, Pellegrini L. An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis. Nat Struct Mol Biol. 2007 14 875-7