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Professor Mark Dillingham

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.