Ubiquitylation pathways controlling the end of chromosome replication

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Our cells contain a molecular machine, known as the ‘replisome’, which makes a precise copy of each of chromosomes before the cell divides in two, so that both of the ‘daughter cells’ contain all of the genetic information that is needed for life. The replisome is very carefully controlled, so that cells only make one single copy of the genetic blueprint that is contained in the chromosomes. If this regulation goes wrong, the results can be lethal in the most extreme case, or else can promote genetic diseases such as cancer. There is much still to learn about the regulation of the replisome. We study how cells destroy the replisome after it has completed its job, by marking the replisome for destruction by a process known as ‘ubiquitylation’. We aim to identify the molecular machines that ubiquitylate the replisome and thus drive its destruction, and we also want to know how this dangerous process is controlled, so that it only happens at the right time. This represents a fundamental issue in cell biology, and is also likely to shed new light on our understanding of cancer development, and potentially might suggest new ideas for future cancer treatments.