Chromosomal DNA replication in eukaryotic cells requires the complex interplay of a large number of essential and non-essential protein factors in a temporally- and spatially-coordinated manner. Determining how these factors act together to replicate the genome is central to understanding how the integrity of the genome is maintained within, and across, generations and how genetic diseases such as cancer are avoided. The components of the replication machinery are also potential targets for anti-proliferative drugs and can be used as diagnostic markers for the proliferative state.
The complexity of the replication machinery favours the use of simple model systems to dissect problems of protein structure, function and regulation. Indeed, much of what we know about the eukaryotic replication apparatus has come from model system studies. In the MacNeill lab, research is focused on dissecting the molecular biology of eukaryotic chromosomal DNA replication and genome stability using two highly contrasting model systems, the eukaryotic fission yeast Schizosaccharomyces pombe and the genetically-tractable halophilic archaeon Haloferax volcanii. We use a variety of methods to address questions of protein structure and function within the chromosome replication apparatus, including genetics and molecular biology, biochemistry, biophysics and bioinformatics.
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