Helicases as modular components of DNA processing machines
Helicases are motor proteins that translocate along and unwind duplex nucleic acids into their component single strands in an ATP-dependent manner. They are exceptionally abundant enzymes and constitute about 1% of the proteome. Accordingly, they are involved in a wide variety of nucleic acid transactions including DNA replication, repair, recombination and transcription and virtually every aspect of RNA metabolism.
An increasing body of evidence suggests that Superfamily I DNA helicases act as modular units that are programmed to fulfil specific cellular tasks by accessory domains and/or interactions with other proteins.
Our research is focused on uncovering the role of such helicases in complex DNA manipulations, such as the processing of broken DNA for repair by homologous recombination. We are also interested in understanding the structural basis for the activation and catalytic modulation of helicase activity that is afforded by interaction with partner proteins. In addition to our work on several model helicases, we are performing exploratory research to identify new helicase partners and are developing novel assays to facilitate our mechanistic studies. We use a wide range of biochemical and biophysical techniques including single molecule methods.
Neville Gilhooly, Dr Emma Gwynn and Dr James Taylor.
Saikrishnan K, Yeeles JT, Gilhooly NS, Krajewski WW, Dillingham MS, Wigley DB. (2012) Insights into Chi recognition from the structure of an AddAB-type helicase-nuclease complex. EMBO Journal. 31(6): 1568-1578.
White MF, Dillingham MS. (2012) Iron-sulphur clusters in nucleic acid processing enzymes. Current Opinion Structural Biology. 22(1):94-100.
Fili N, Toseland CP, Dillingham MS, Webb MR, Molloy JE. (2011) A single-molecule approach to visualize the unwinding activity of DNA helicases. Methods in Molecular Biology. 778:193-214.
Yeeles JT, van Aelst K, Dillingham MS, Moreno-Herrero F. (2011) Recombination hotspots and single-stranded DNA binding proteins couple DNA translocation to DNA unwinding by the AddAB helicase-nuclease. Molecular Cell. 42(6):806-16.