Office Room D.46
Biomedical Sciences Building,
University Walk,
Clifton
BS8 1TD
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+44 (0) 117 3312159
mark.dillingham@
bristol.ac.uk
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. Our research is focused on uncovering the role of such helicases in complex DNA manipulations, including the processing of broken DNA for repair by homologous recombination and the resolution of conflicts between DNA replication and transcription.
Figure: AddAB helicase-nuclease bound to a DNA break (Saikrishnan et al., EMBO J. 2012, 31, 1568)
Chromosome dynamics
Genetic information is commonly stored in very large DNA molecules called chromosomes. These molecules must be efficiently condensed and segregated into daughter cells within the confines of a crowded cell. Remarkably, a whole myriad of other DNA transactions including transcription and repair occur simultaneously on the same molecule. Using Bacillus subtilis as a model system, we are studying the co-ordination of DNA replication, condensation and segregation, with a particular emphasis on the role of structural maintenance of chromosomes (SMC) proteins.
Figure: V- and O-shaped SMC proteins imaged by atomic force microscopy (Fuentes-Perez et al. Biophys. J., 2012, 102, 839)
Join our group!
We are always interested in hearing from talented scientists who wish to join the laboratory. Please contact Mark Dillingham for an informal discussion of the opportunities that are currently available.
Mark Dillingham's research is in the field of DNA:protein interactions. He obtained his D. Phil. in Oxford with Dale Wigley studying the structure and mechanism of DNA helicases. This research was developed further in postdoctoral study at the University of California at Davis (with Steve Kowalczykowski) and at the National Institute for Medical Research (with Martin Webb) which focused on how helicase motors were integrated into larger machines, such as those responsible for the repair of double-stranded DNA breaks.
The Dillingham laboratory was established in Bristol in 2005. Recent and current work has focussed on the mechanisms of double-stranded DNA break repair, transcription:replication conflicts and chromosome segregation (see research interests for further details). This work has been supported by major grant funding and fellowships from the Royal Society, the European Research Council and the Wellcome Trust. Mark was awarded the Colworth medal of the Biochemical Society in 2010.
Macromolecular Structure, Dynamics and Function
Molecular Genetics
Recombinant DNA Technology
Protein Assemblies and Molecular Machines
Research Training
Cellular Information
Advanced Options in Biochemistry – DNA
Biophysics and Molecular Life Sciences I
Biophysics and Molecular Life Sciences II
MSc Core Skills
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, afforded by interaction with partner proteins.
View complete publications list in the University of Bristol publications system
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