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Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor Jan 2010

Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor

Wayne State University Dissertations

Progression through meiosis occurs through a strict sequence of events, so that one round of DNA replication precedes programmed recombination and two nuclear divisions. Cyclin dependent kinase 1 (Cdk1) is required for meiosis, and any disruption in its activity leads to meiotic defects. The Cdk1 inhibitor, Sic1, regulates the G1-S transition in the mitotic cell cycle and the analogous transition in meiosis. We have employed a form of Sic1, Sic1deltaPHA, that is mutated at multiple phosphorylation sites and resistant to degradation. Meiosis specific expression of Sic1deltaPHA disrupts Cdk1 activity and leads to significant accumulation of over replicated …


Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan Jan 2010

Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan

Wayne State University Dissertations

Sin3A has been previously shown to be an essential gene for Drosophila viability and is implicated in the regulation of cell cycle. In this study, we show that SIN3 is not only required for embryonic viability but also for post-embryonic development. Genetic analysis suggests that the different isoforms of SIN3 may regulate unique sets of genes during development. The developmental lethality occurring due to ubiquitous knock down of SIN3 is hypothesized to be to the result of defects in cell proliferation. Conditional knock down of SIN3 in the wing discs results in a curly wing phenotype in the adult fly. …


Determination Of The Essential Functions Of A Conserved Cyclin, Cyclin Y, In Drosophila, Dongmei Liu Jan 2010

Determination Of The Essential Functions Of A Conserved Cyclin, Cyclin Y, In Drosophila, Dongmei Liu

Wayne State University Dissertations

The Drosophila gene CG14939 encodes a member of a highly conserved family of cyclins, the Y type cyclins, which have not been functionally characterized in any organism. Here I report the generation and phenotypic characterization of a null mutant of CG14939, which we rename Cyclin Y (CycY). I show that the null mutant, CycYE8, is homozygous lethal with most mutant animals arresting during pupal development. The mutant exhibits delayed larval growth and major developmental defects during metamorphosis. Heat shock-induced expression of CycY at different times during development resulted in variable levels of rescue, the timing …


Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development, John Hunt Lillvis Jan 2010

Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development, John Hunt Lillvis

Wayne State University Dissertations

Abdominal aortic aneurysm (AAA) is a common disease for which mechanisms of formation are still not well understood. Despite a strong genetic component to AAA risk, specific risk alleles are still largely unidentified. AAA is also a localized disease with a majority occurring in the infrarenal abdominal aorta and is six times more common than aneurysms of the thoracic aorta. To determine whether risk alleles are present in functional positional candidate genes. we: 1. performed a genetic association study using DNA from AAA cases and controls in ten candidate genes and 2. performed exon sequencing on three genes with evidence …


Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson Jan 2010

Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson

Wayne State University Dissertations

The dominant paradigm for cancer research focuses on the identification of specific genes for cancer causation and for the discovery of therapeutic targets. Alternatively, the current data emphasize the significance of karyotype heterogeneity in cancer progression over specific gene-based causes of cancer. Variability of a magnitude significant to shift cell populations from homogeneous diploid cells to a mosaic of structural and numerical chromosome alterations reflects the characteristic low-fidelity genome transfer of cancer cell populations. This transition marks the departure from micro-evolutionary gene-level change to macro-evolutionary change that facilitates the generation of many unique karyotypes within a cell population. Considering cancer …