Professor Dale Wigley FRS
Academic Title: Professor of Protein Crystallography
Tel: 020 7153 5521
Location: Chester Beatty Laboratories, London
Every cell experiences tens of thousands of DNA damage events (lesions) every day. Unless these are faithfully repaired, mutations can occur which can lead to cancer. Our research programme focuses in two areas: the repair of double-strand DNA breaks, and chromatin remodelling events that take place in response to DNA damage.
In bacteria, double-strand DNA breaks are processed by the RecBCD and AddAB complexes these convert the end to a 3’-tailed duplex which is coated in the RecA recombinase protein that then initiates repair via homologous recombination.
In humans, similar enzyme systems exist that achieve the same goal by processing the DNA break and forming a Rad51 filament that then initiates recombination. We are studying the structure and mechanism of the RecBCD and AddAB complexes alongside the equivalent human protein complexes to understand this fundamental process in DNA repair.
In eukaryotes, the DNA is packaged into nucleosomes within which the DNA is wrapped around a histone octamer core. If the DNA within a nucleosome becomes damaged, this then has to be detected and then repaired. In order to gain access to the DNA lesion, the histone core has to be shifted along the DNA in order to expose the damage to repair enzyme systems by a process called chromatin remodelling. We are working to understand how these complex macromolecular chromatin remodelling machines drive this process.
After a BSc in Biochemistry at the University of York, Professor Wigley studied for his PhD at the University of Bristol. Post-doctoral work at the Universities of Leicester and York was followed by his appointment to a Lectureship in Molecular Biophysics at Oxford University in 1993. He was made a Reader in 1997.
In 2000, Professor Wigley took a position as Principal Scientist at the CRUK London Research Institute; he then joined The Institute of Cancer Research as Joint Head of the Division of Structural Biology in 2010.
Professor Wigley was elected as a member of the European Molecular Biology Organisation (EMBO) in 2002 and a Fellow of the Royal Society in 2004. Over his entire career, Professor Wigley has maintained an interest in the structure and mechanism of enzymes, with a particular focus on proteins involved in DNA replication and repair. This work is currently funded by Cancer Research UK and the Wellcome Trust.
Modification of Chromatin
We aim to understand the structure and mechanism of a number of different multi-subunit complexes that regulate chromatin.
Repair of DNA double-strand breaks
The aims of this project are to understand the structure and mechanism of the processing of double-strand DNA breaks as a prelude to recombination repair