Dr Stuart MacNeill

SULSA Reader in Translational Biology

BMS B306
tel. 01334 467268
fax. 01334 462595
sam31@st-andrews.ac.uk

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 molecular mechanisms of chromosomal DNA replication and genome stability in eukaryotic cells using two highly contrasting genetically tractable model systems, the eukaryotic fission yeast Schizosaccharomyces pombe and the halophilic euryarchaeon 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. In addition, the group has recently begun to isolate and characterise protein complexes predicted to be essential for nuclear DNA replication in the parasitic protozoan Trypanosoma brucei, the causitive agent of African sleeping sickness, with a view towards screening for small molecule inhibitors of their functions as a starting point on the journey towards the development of novel anti-trypanosomal therapeutics.

 

Publications

Varnaitė , R & MacNeill, SA 2016, 'Meet the neighbours: mapping local protein interactomes by proximity-dependent labelling with BioID' Proteomics, vol 16, no. 19, pp. 2503-2518. DOI: 10.1002/pmic.201600123
MacNeill, SA 2016, 'PCNA-binding proteins in the archaea: novel functionality beyond the conserved core' Current Genetics, vol 62, no. 3, pp. 527-532. DOI: 10.1007/s00294-016-0577-3
Giroux, X & MacNeill, S 2015, 'Inhibiting NAD+-dependent DNA ligase activity with 2-(cyclopentyloxy)-5'-deoxyadenosine (CPOdA) offers a new tool for DNA replication and repair studies in the model archaeon Haloferax volcanii' FEMS Microbiology Letters, vol 362, no. 21, fnv181. DOI: 10.1093/femsle/fnv181
Giroux, X & MacNeill, S 2015, 'A novel archaeal DNA repair factor that acts with the UvrABC system to repair mitomycin C-induced DNA damage in a PCNA-dependent manner' Molecular Microbiology. DOI: 10.1111/mmi.13210
Giroux, X & MacNeill, S 2015, 'Molecular genetic methods to study DNA replication protein function in Haloferax volcanii, a model archaeal organism.' Methods in Molecular Biology, vol 1300, pp. 187-218. DOI: 10.1007/978-1-4939-2596-4_13
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