Date of Award

2014

Degree Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

First Advisor

Hudson, John W.

Keywords

Biological sciences, Blood disorders, Dna damage, Epigenetics, Methylation, Plk, Polo-like kinase 4

Rights

CC BY-NC-ND 4.0

Abstract

The evolutionarily conserved polo-like kinases (PLKs) are pivotal cellular proteins that govern mitotic progression, DNA damage, centrosome replication, and neuronal processes. Appropriate expression of these serine/threonine kinases is essential for cellular homeostasis as perturbations to PLK expression often results in oncogenic transformation and tumor development. In addition to loss of heterozygosity, the PLKs are also susceptible to aberrant epigenetic modifications in tumorigenic states. My studies describe the deregulation of the PLKs in the context of hematological malignancies and provide support that the methylation-dependent dysregulation may possess diagnostic and prognostic value. Moreover, I have characterized novel interacting substrates (PRMT5 and GADD45a) and interacting partners (Nucleophosmin and JAK2) of PLK4, a polo family member with tumor suppressive functions. These novel interactions implicate PLK4 in epigenetic and DNA damage regulatory pathways that may be essential to preserve and maintain centrosome and genomic integrity.

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