Research groups

Research

Helicases as modular components of DNA processing machines

RecBCD helicase-nuclease bound to a DNA break.

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.

Group

Neville Gilhooly, Dr Emma Gwynn and Dr Kara van Aelst.

Recent publications

Fili, N., Mashanov, G.I., Toseland, C.P., Batters, C., Wallace, M.I., Yeeles, J.T.P., Dillingham, M.S., Webb, M.R. and Molloy, J.E. (2010) Visualizing helicases unwinding DNA at the single molecule level. Nucl. Acids Res., Epub March 2010

Yeeles, J.T. and Dillingham, M.S. (2010) The processing of double-stranded DNA breaks for recombinational repair by helicase-nuclease complexes.DNA Repair (Amst)., 9, 276-285.

Guy, C.P., Atkinson, J., Gupta, M.K., Mahdi, A.A., Gwynn, E.J., Rudolph, C.J., Moon, P.B., van Knippenberg, I.C., Cadman, C.J., Dillingham, M.S., Lloyd, R.G. and McGlynn, P. (2009) Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA. Molecular Cell, 36, 654-666.

Manelyte, L., Guy, C.P., Smith, R.M., Dillingham, M.S., McGlynn, P. and Savery, N.J. (2009) The unstructured C-terminal extension of UvrD interacts with UvrB, but is dispensable for nucleotide excision repair. DNA Repair, 8, 1300-1310.