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.
Our research aims to define structural and functional properties of proteins and protein complexes responsible for the maintenance and replication of our genome. Our experimental approach involves the reconstitution in vitro of the biological system under investigation, which can then be subject to biochemical and biophysical analysis. We work on processes that pertain to both DNA repair and replication. Please see our publication list below for more information.
Our research is funded by the Wellcome Trust and the Medical Research Council.
Lab members: Joseph Maman, Mairi Kilkenny, Neil Rzechorzek, Laura Radu, Johanna Syrianen, Sandro Holzer, Christopher Morton, Aji Jatikusumo, Yue Zhang.
Enquiries from talented and motivated students wishing to pursue a PhD in our lab are always welcome.
Villa F, Simon AC, Ortiz Bazan MA, Kilkenny ML, Wirthensohn D, Wightman M, Matak-Vinkovíc D, Pellegrini L, Labib K. Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase. Mol Cell. 2016 63:385-96. PMID: 27397685.
Simon AC, Sannino V, Costanzo V, Pellegrini L. Structure of human Cdc45 and implications for CMG helicase function. Nat Commun. 2016 7:11638. PubMed PMID: 27189187; PubMed Central PMCID: PMC4873980.
Davies OR, Forment JV, Belotserkovskaya R, Coates J, Galanty Y, Demir M, Morton CR, Rzechorzek NJ, Jackson SP, Pellegrini L. CtIP tetramer assembly is required for DNA-end resection and repair. Nat Struct Mol Biol. 2015 22:150-7.
Rzechorzek NJ, Blackwood JK, Bray SM, Maman JD, Pellegrini L, Robinson NP. Structure of the hexameric HerA ATPase reveals a mechanism of translocation-coupled DNA-end processing in archaea. Nat Commun. 2014 5:5506.
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.
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