Regulation of RCC1 through N-terminal serine metnylation

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DESCRIPTION (provided by applicant): RCC1 is the nucleotide exchange factor for the small, Ras-like GTPase Ran. It is involved in many cellular processes including spindle assembly and spindle checkpoint regulation, that when misregulated can lead to cellular transformation and carcinogenesis. Determining how RCC1 is regulated will more clearly define how spindle assembly and checkpoint regulation are controlled and further the development of anticancer therapeutics targeted against these processes. A novel post-translational modification of RCC1, N-terminal serine methylation, has recently been identified in the Macara lab, and this proposal will examine its role in the regulation of RCC1 function. Specific aim #1 will determine which aspects of RCC1 function N-terminal serine methylation affects and how it regulates these functions. Specific aim #2 will identify the methyltransferase responsible for the N-terminal serine methylation of RCC1.