The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Dale Wigley : Molecular Enzymology
The Molecular Enzymology Laboratory headed by Dale Wigley aimed to understand the molecular basis for enzyme activity in DNA replication and repair processes. The laboratory was established at Clare Hall Laboratories in 2000 and closed in 2010.
Accessibility of DNA within chromatin is essential for a variety of biological processes from transcription to DNA replication and repair. It has become evident that protein systems are present in cells that regulate accessibility of DNA by remodelling the nucleosomes. Typically, these remodelling complexes comprise several proteins assembled around a central protein whose function is to translocate along double-stranded DNA in an ATP-dependent manner and thereby move the nucleosomes along the DNA (or unwrap the DNA to allow access and/or exchange histone proteins). Classification of the chromatin remodelling translocases reveals at least four protein families. These translocase proteins are related to DNA helicases of Superfamily 2 (SF2). Although considerable advances have been made towards understanding the mechanism of single-strand translocation by Superfamily 1 and SF2 helicases, rather less is understood about double-strand translocases. Even less is known about the complex mechanism by which these enzymes, together with other proteins, are able to remodel nucleosomes.
Dale left the LRI to join the Institute of Cancer Research in London, UK.
Significant Papers LRI
- Saikrishnan K, Powell B, Cook N, Webb MR, Wigley DB. Mechanistic basis of 5’-3’ translocation in SF1B helicases. Cell. 2009;137:849-859 (Abstract)
- Gaudier M, Schuwirth BS, Westcott SL, Wigley, DB. Structural basis of DNA replication origin recognition by an ORC protein. Science. 2007;317:1213-1216 (Abstract)
- Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Ann. Rev. Biochem. 2007;76:23-50 (Abstract)
- Singleton MR, Dillingham MS, Gaudier M, Kowalczykowski SC, Wigley DB. Crystal structure of RecBCD reveals a machine for processing DNA breaks. Nature. 2004;432:187-193 (Abstract)