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Regulation Of Yolk Microtubule Dynamics By Dachsous Cadherins, Gina Danielle Castelvecchi Aug 2020

Regulation Of Yolk Microtubule Dynamics By Dachsous Cadherins, Gina Danielle Castelvecchi

Arts & Sciences Electronic Theses and Dissertations

The process of epiboly, or the thinning and spreading of a tissue, is a well-conserved morphogenetic process. As one of four conserved gastrulation cell movements, epiboly is important to help organize the overall body plan. Epiboly in zebrafish involves the thinning and spreading of the blastoderm originating from the animal pole to completely enclose the yolk. It is driven by a multitude of physical processes that involve the three cell types comprising the embryo: the yolk syncytial layer (YSL), enveloping layer (EVL), and deep cells. These physical aspects can be broadly described as involving cell-cell interactions through adhesion proteins, actomyosin …


Assessing The Role Of Ku70 Vwa Domain Phosphorylation In The Inhibition Of Aurora B And Activation Of The Dna Damage Response, Elizabeth A. Walden Apr 2017

Assessing The Role Of Ku70 Vwa Domain Phosphorylation In The Inhibition Of Aurora B And Activation Of The Dna Damage Response, Elizabeth A. Walden

Electronic Thesis and Dissertation Repository

Ku is a key component of the Non-Homologous End Joining DNA repair pathway. Recently, a function for Ku in DNA damage response (DDR) signalling was identified through studies exploring a Ku70 S155D phosphomimetic mutant. We hypothesize that Ku70 S155D mimics phosphorylation of Ku70 in response to DNA damage, and that Ku S155 phosphorylation inhibits Aurora B and causes sustained DDR activation. In this study we show that the S155D mutant is competent for heterodimerization, and its expression does not induce DNA damage. Phosphorylated Ku70 associates with Aurora B by co-immunoprecipitation and this association was demonstrated in situ with Ku70 S155D. …


The Role Of The Ku70 Vwa Domain In The Response To Dna Double Strand Breaks, Victoria L. Fell Nov 2014

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 …


A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully May 2011

A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully

Dissertations & Theses (Open Access)

The mitotic kinase Aurora B plays a pivotal role in mitosis and cytokinesis and governs the spindle assembly checkpoint which ensures correct chromosome segregation and normal progression through mitosis. Aurora B is overexpressed in breast and other cancers and may be an important molecular target for chemotherapy. Tumor suppressor p53 is the guardian of the genome and an important negative regulator of the cell cycle. Previously, it was unknown whether Aurora B and p53 had mutual regulation during the cell cycle. A small molecule specific inhibitor of Aurora B, AZD1152, gave us an indication that Aurora B negatively impacted p53 …


Characterization Of A Novel Chromatin‐Induced Mechanism That Couples Microtubule Disassembly And Nuclear Re‐Formation, Eileen Madeleine Woo Jan 2010

Characterization Of A Novel Chromatin‐Induced Mechanism That Couples Microtubule Disassembly And Nuclear Re‐Formation, Eileen Madeleine Woo

Student Theses and Dissertations

Upon completion of mitosis, the disassembly of spindle components and reassembly of nuclear structures occur simultaneously around chromatin. Previous studies have suggested that an important step in this process is the inactivation of the Aurora B kinase by the Triple A‐ATPase Cdc48/p97, which physically extracts the protein from chromatin at anaphase. Aurora B is the catalytic subunit of the Chromosome Passenger Complex (CPC), which promotes microtubule polymerization and spindle formation from mitotic chromosomes. Removal of the CPC from chromosomes at anaphase is required for proper nuclear reassembly, but the molecular basis for this requirement remains unclear. On the whole, the …


Regulation Of Chromosome Segregation By The Chromosomal Passenger Complex, Boo Shan Tseng Jan 2010

Regulation Of Chromosome Segregation By The Chromosomal Passenger Complex, Boo Shan Tseng

Student Theses and Dissertations

Life depends on faithful DNA segregation. The molecular underpinnings controlling this segregation are not fully understood. Here I describe the role of the chromosomal passenger complex (CPC) in the regulation of chromosome segregation, using Xenopus egg extracts. The CPC contains the kinase Aurora B, which is well known for its phosphorylation of serine 10 on histone H3 (H3S10). While this phosphorylation is a hallmark of M-phase, its functional significance is enigmatic. In the first part of my thesis, I, with my collaborators, provide a molecular function for this phosphorylation in the chromosomal dissociation of HP1 (heterochromatin protein 1) in M-phase. …


Control Of Chromosome Segregation By The Aurora B Complex, Srinath Cidambi Sampath Jan 2006

Control Of Chromosome Segregation By The Aurora B Complex, Srinath Cidambi Sampath

Student Theses and Dissertations

Chromosome segregation during cell division requires spindle assembly around M-phase chromatin. In cells lacking centrosomes, such as those found in female meiosis, chromosomes themselves nucleate and stabilize microtubules in order to promote accurate spindle formation. Here we present a description of the composition and function of the vertebrate chromosomal passenger complex (CPC), known to include Incenp, Survivin, and the kinase Aurora B. We report the identification of Dasra A and Dasra B as two new components of the vertebrate CPC, and demonstrate that the CPC is required for chromatin-dependent spindle formation in Xenopus egg extracts. The failure of microtubule stabilization …