Investigating mechanisms of eukaryotic chromosome replication
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We each synthesise approximately 1 million kilometres of DNA per minute, over 20 times the circumference of planet Earth. The cellular machinery responsible for this remarkable feat is called the replisome. The eukaryotic replisome is a large, sophisticated and highly regulated molecular machine that possesses all of the activities required for rapid and accurate chromosome replication.
Biochemical reconstitution with purified proteins has proved to be a hugely powerful approach to study mechanisms of chromosome replication. Until recently however, much of our knowledge was based on experiments using prokaryotic or viral replication systems because a fully reconstituted eukaryotic replication system had proved to be elusive. I have recently reconstituted for the first time the regulated assembly of the eukaryotic replisome with purified proteins from budding yeast1. The development of this system marks the beginning of a new era in the study of eukaryotic chromosome replication and enables us to address important questions in ways that were not previously possible.
We are looking for an ambitious and enthusiastic student to join our research group. During your PhD you will further develop the reconstituted system and use it to uncover and characterise novel mechanisms of eukaryotic chromosome replication. During your PhD you will become an expert in protein purification and complex biochemical reconstitution, while also gaining experience in yeast genetics and molecular biology. Our small group provides an excellent environment to learn new techniques, both directly from myself and from experienced post docs in the lab, whilst working on an independent project.
Yeeles, J.T., Deegan, T.D., Janska, A., Early, A. and Diffley, J.F. (2015)
Regulated eukaryotic DNA replication origin firing with purified proteins.
Nature 519(7544): 431-435
Yeeles, J.T. and Marians, K.J. (2011)
The Escherichia coli replisome is inherently DNA damage tolerant.
Science 334(6053): 235-238