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Investigation of mechanisms of mitotic recombination in yeast

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dc.contributor.authorHarcy, Lisa Victoria, author
dc.contributor.authorArgueso, Lucas, advisor
dc.contributor.authorDi Pietro, Santiago, committee member
dc.contributor.authorLiber, Howard, committee member
dc.contributor.authorSuchman, Erica, committee member
dc.date.accessioned2016-08-18T23:11:33Z
dc.date.available2016-08-18T23:11:33Z
dc.date.issued2016
dc.description.abstractAt the submicroscopic level within all living cells the workings of a dynamic molecular world attempt to preserve the integrity of DNA - the blueprint of life. This dissertation describes in detail the experimental systems and results from two of our studies conducted in which DNA lesions compromised genomic integrity. The unifying theme of the following chapters revolves around the mechanisms responsible for structural genomic variation, that is, what happens to chromosomes when they break. In the first phase of research, we examined outcomes associated with double-strand breaks (DSBs) at G-quadruplex DNA sequences. Here, we show that G4 DNA motifs, capable of initiating double-strand breaks, result in the formation of chromosomal aberrations. Our results provide structural context and support to a putative mechanism of homology-directed repair revealed by molecular analysis of these complex rearrangements. In the second project, we investigated chromosomal translocations that developed from spontaneously occurring DSBs in diploid yeast to ascertain the means by which the DSBs had been repaired. The objective of this study was to examine the intricate interplay between the non-allelic DSB repair (DSBR) processes: canonical reciprocal homologous recombination (CRHR) vs. break-induced replication (BIR). While numerous assays have previously measured repair pathway efficiency by isolating one of the two pathways from the other, no prior studies to our knowledge, have prospectively examined the contribution of BIR to overall double-strand break repair in diploids, using a non-inducible experimental system where either mechanism can be used freely by the cells. I designed and constructed a new assay system to study chromosomal translocations in the yeast eukaryotic model to investigate the balance between these two DSB repair processes. I characterized genotypic and phenotypic alterations in wild type background and in mutant yeast strains defective for BIR. The data obtained from this work provides an additional perspective to the field of DNA repair biology with broad relevance to DSBR regulation in eukaryotes. It provides further understanding about the role of DNA repair to undesired genetic outcomes, thus, leading the way to the design of new and more effective treatments for diseases in which these molecular actions are the instigators of pathogenesis.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierHarcy_colostate_0053A_13783.pdf
dc.identifier.urihttp://hdl.handle.net/10217/176742
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.relation.referencesYadav, Puda, Victoria Harcy, Juan Lucas Argueso, Margaret Dominska, Sue Jinks-Robertson, Nayun Kim, Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence. PLoS Genetics 10, no. 12 (December 2014): e1004839. http://dx.doi.org/10.1371/journal.pgen.1004839
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectchromosomal rearrangement
dc.subjectgenome stability
dc.subjectnon-reciprocal translocation
dc.subjectbreak-induced replication
dc.subjectg-quadruplex
dc.subject.lcshDNA repair
dc.titleInvestigation of mechanisms of mitotic recombination in yeast
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineCell and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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