Joseph Yeeles

Joseph Yeeles

Mechanisms of chromosome replication

jyeeles@mrc-lmb.cam.ac.uk

Precise chromosome replication is essential for maintaining genome stability, yet the process itself is inherently risky. Duplex DNA must be transiently separated into unstable single-strands; a vast number of DNA bases must be accurately copied; and replication forks frequently encounter protein barriers and unrepaired DNA damage that can stall and even derail the replication machinery (replisome).

Our lab is interested in mechanisms of chromosome replication, and how these mechanisms contribute to faithful genome duplication.

Regulated assembly of a minimal eukaryotic replisome with purified proteins
Figure modified from Yeeles, J.T., Deegan, T.D., Janska, A., Early, A. and Diffley, J.F. (2015) Nature 519(7544): 431-435, with permission from J Diffley.

The eukaryotic replisome is a highly complex molecular machine that is assembled from in excess of 30 gene products and which orchestrates the activities of multiple enzymatic components. To study this remarkable machine in action our lab reconstitutes replication in vitro using purified proteins. This highly defined experimental system, used in conjunction with genetic approaches and replication proficient cell-free extracts, enables us to investigate fundamental aspects of replisome biology.

Selected Papers

Group Members

  • Domagoj Baretic
  • Martin Taylor
  • Valentina Aria
  • Tom Guilliam
  • Michael Jenkyn-Bedford