Molecular Biology Commons^™

The Epigenetic Regulators Atrx And Ctcf Are Required For Mouse Neuroprogenitor Cell Survival And Brain Development, Lauren Ashley Watson

Electronic Thesis and Dissertation Repository

Emerging evidence implicates the regulation of higher-order chromatin structure in brain development, maturation, and function. Human mutations in two important regulators of chromatin structure, ATRX and CTCF, cause microcephaly and intellectual disability and have been identified in several cancers, suggesting an important role for these proteins in the developing brain and to suppress tumorigenesis. This thesis demonstrates that chromatin structure is critical to the differentiation and survival of neural progenitor cells, and explores the mechanisms of ATRX and CTCF function in brain development. The first chapter identifies that Atrx deficiency induces replicative DNA damage at telomeres and pericentromeric heterochromatin, and …

The Role Of The Ku70 Vwa Domain In The Response To Dna Double Strand Breaks, Victoria L. Fell

Electronic Thesis and Dissertation Repository

Ku is an abundant, highly conserved DNA binding protein found in both prokaryotes and eukaryotes that plays essential roles in the maintenance of genome integrity. In eukaryotes, Ku is a heterodimer comprised of two subunits, Ku70 and Ku80, and is best characterized for its central role as the initial DNA end binding factor in the “classical” non-homologous end joining (C-NHEJ) pathway, the main DNA double-strand break (DSB) repair pathway in mammals. At the break, Ku directly and indirectly interacts with several C-NHEJ factors and processing enzymes, serving as the scaffold for the entire DNA repair complex. In this work we …

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that …