Our laboratory studies .....

The process of chromosome resolution. During chromosome replication the sister chromatids become entangled. All such entanglements need to be resolved before the chromosomes can be faithfully segregated to the daughter cells during mitosis. In particular we study how the induction of topological stress into the DNA results in the generation of double stranded intertwines or catenanes during the termination phase of DNA replication and conversely how the introduction of DNA supercoiling in G2 and mitosis drives the resolution of all such catenanes before chromosome segregation.

 Failure to resolve chromosomes leads to the daughter cells not having the normal complement of genetic information. This leads to either cell death or widespread genomic instability – a potential pathway to cancer.

 We principally tackle these issues in the budding yeast system. The sophisticated genetics available in this model organism allows careful dissection of the pathways involved in chromosome resolution. This produces detailed and coherent mechanisms for the action of these pathways that can then be tested in more intractable mammalian cells.

Our research work is funded by: