Accurate DNA replication is essential for genome stability. The successful creation of new, healthy cells relies on proper function of replication protein complexes, which must have effective methods for both recognizing and responding to replication stress. Replication stress arises from many different sources, but can be broadly defined as the slowing or stalling of replication forks1. One way replication proteins chemically communicate is through post-translational modifications (PTMs) in which their functions are altered by the attachment and removal of chemical groups or small peptide chains. Attachment of Small Ubiquitin-like Modifiers (SUMOs) to target proteins is a type of PTM. SUMO chains are “read” or recognized by SUMO-Interacting Motifs, and SUMO-SIM interaction can promote the formation of stable protein complexes2. Previous work of Yee-Mon Thu, Ph.D., and other members of the Bielinsky Laboratory has shown that SUMOylation is required for the survival of Saccharomyces cerevisiae cells containing mutations of their Mcm10 replication proteins, which creates a steady source of replication stress within the cells3. Of particular interest was the finding that protein subunits of a complex called chromosome passenger complex (CPC) had different levels of SUMOylation between mcm10-1 mutant cells and wild type cells. CPC is responsible for regulating mitosis4, and we hypothesized that CPC subunits contain SIMs and SUMO consensus sequences. To test this hypothesis, bioinformatics software was used to find potential SIMs on protein subunits of yeast CPC based on primary structures, and mutants of one particular CPC subunit called Bir1 are currently being studied. Additionally, we used bioinformatics to predict several potential SIMs in Homo sapiens CPC, creating opportunity for further laboratory testing. Understanding the functional significance of SIMs in CPC subunits can provide insights into how SUMO regulates cell cycle progression and diverse cellular processes.
This research was conducted during the Spring 2015 semester through the support of an Undergraduate Research Scholarship through the Undergraduate Research Opportunities Program.
Hedberg, Jack P.
The Role of Small Ubiquitin-like Modifiers and SUMO-Interacting Motifs in Replication Stress.
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