Date of Award
2014
Publication Type
Master Thesis
Degree Name
M.Sc.
Department
Biological Sciences
Keywords
Biological sciences, Blood disorders, Dna damage, Epigenetics, Methylation, Plk, Polo-like kinase 4
Supervisor
Hudson, John W.
Rights
info:eu-repo/semantics/openAccess
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
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.
Recommended Citation
Sivakumar, Gayathri, "Polo-like kinase 4 at the nexus of epigenetic modifications and the DNA damage signaling network" (2014). Electronic Theses and Dissertations. 5146.
https://scholar.uwindsor.ca/etd/5146