Investigating the roles of ubiquitin and SUMO during eukaryotic chromosal replication

Priego Moreno, Sara (2017). Investigating the roles of ubiquitin and SUMO during eukaryotic chromosal replication. University of Birmingham. Ph.D.

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Abstract

Genome duplication is an essential cellular process and its appropriate execution is required to maintain genome integrity. Ubiquitin and SUMO belong to the protein family of ubiquitin-like modifiers, and they are required to maintain genome integrity by acting as key regulators in the response to DNA damage. However, their role in the regulation of unperturbed DNA replication is less understood. My PhD work has focused on studying the roles of ubiquitin and SUMO during unperturbed DNA replication in Xenopus laevis egg extract.
Members of our lab showed that polyubiquitylation of Mcm7 – a subunit of the CMG replicative helicase, promoted CMG disassembly during DNA replication termination. Importantly, my work identified the ubiquitin ligase cullin2LRR1 as the enzyme required for Mcm7 polyubiquitylation and CMG disassembly. I also showed that these events were restricted to termination by the regulated recruitment of cullin2LRR1 to the terminated replisome. Moreover, I showed that the p97 protein remodeller was recruited to the polyubiquitylated CMG and drove chromatin extraction of the terminated replisome.
My work has also provided the first insights into how the chromatin associated proteome changes in response to impaired sumoylation during S phase. Finally, I have identified several potential SUMO2 substrates associated with replicating chromatin.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):