Examining genome stability during DNA replication, using the hyperthermophilic archaeon, Sulfolobus, as a model organism.
The complete and accurate duplication of the genetic material prior to cell division is a
prerequisite for life. Maintaining genomic stability during this replication process is both
complex and remarkable, and a multitude of repair pathways and machineries exist to
repair damage to the template, and ensure faithful copying of the genome. Chromosomal
instability is a hallmark of cancer, and it is therefore clear that the regulation of genomic
integrity is crucial for the prevention of human genetic disease.
In my laboratory, we use the hyperthermophilic archaeon, Sulfolobus, as a model
organism to examine DNA repair events that occur during DNA replication. Although these
ancient microbes are phylogenetically distinct from both bacterial and eukaryotic cells,
there is nevertheless a remarkable similarity between the archaeal and eukaryotic DNA
replication and repair apparatus. In addition, proteins isolated from hyperthermophilic
archaea such as Sulfolobus, demonstrate an intrinsic thermostability, that greatly
facilitates their purification and biochemical analysis. Thus, Sulfolobus represents an ideal
organism for examining basic eukaryotic-like DNA replication and repair processes.
This work will examine the processes implicated in the prevention of replication fork
collapse, following template damage, and will also investigate the mechanisms involved in
restarting forks that become blocked during replication. A variety of in vitro biochemical
techniques will be employed, along with in vivo and genetic approaches, to explore the
role of candidate proteins in replication-related repair. It is likely that this work will
provide insights into the basics of fork repair mechanisms used in more complex
Robinson, N. P., K. A. Blood, S. A. McCallum, P. A. Edwards, and S. D. Bell. 2007. Sister chromatid junctions in the hyperthermophilic archaeon Sulfolobus solfataricus. Embo J 26:816-24.
Robinson, N. P., and S. D. Bell. 2007. Extrachromosomal element capture and the evolution of multiple replication origins in archaeal chromosomes. Proc Natl Acad Sci U S A 104:5806-11.
Robinson, N. P., I. Dionne, M. Lundgren, V. L. Marsh, R. Bernander, and S. D. Bell. 2004. Identification of two origins of replication in the single chromosome of the archaeon Sulfolobus solfataricus. Cell 116:25-38.