Eukaryotic cells can efficiently detect and repair DNA double-strand breaks (DSBs) arising from exposure to toxic agents or as intermediates of nucleic acid metabolism.
Failure of the DSB repair apparatus to restore the integrity of damaged chromosomes is a major contributing factor in human disease. The goal of our research is to define atomic structure and mechanism of action of the macromolecular assemblies responsible for signalling and processing of DNA DSBs.
Lab members
Owen Davies, Sebastian Klinge, Mike Longo, Joseph Maman, Ravi Nookala, Stefania Ragone, Neil Rzechorzek
References
Klinge S, Núñez-Ramírez R, Llorca O, Pellegrini L. "3D architecture of DNA Pol alpha reveals the functional core of multi-subunit replicative polymerases." EMBO J. 2009 Jul 8;28(13):1978-87.
Ragone S, Maman JD, Furnham N, Pellegrini L. "Structural basis for inhibition of homologous recombination by the RecX protein." EMBO J. 2008 Aug 20;27(16):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 Sep;14(9):875-7.
Davies OR, Pellegrini L. "Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats." Nat Struct Mol Biol. 2007 Jun;14(6):475-83.