Global ETD Search

1	Reporter-based Synthetic Genetic Analysis of Budding Yeast Reveals Novel MMS-induced Effectors of the RNR3 Promoter Elnour, Nada January 2016 (has links) The DNA damage response is a cell-wide response that coordinates repair and cell-cycle progression. Crucial to fidelity of genetic propagation, survival, and apoptosis, dysfunctions in the response are at the root of genome instability syndromes and cancer predisposition in mammalian cells. Within the response lie hubs of coordination, called checkpoints, whose members and organization are ubiquitous amongst eukaryotes. The high conservation of these checkpoints enable the study of their dynamics by proxy via simpler model organisms. We use the budding yeast, Saccharomyces cerevisiae, to study the replication and DNA damage checkpoints --- both implicated in DNA damage repair. Using a yEGFP reporter driven by the RNR3 promoter and reporter-based synthetic genetic array analysis, we created a detector of potential checkpoint activation in response to two doses of MMS, 0.015% and 0.060% (v/v). The high-throughput screens and differential epistasis miniarray analyses (EMAPs) yield unanticipated involvement of oxidative stress response, ribosomal biogenesis, and chromatin remodelling genes. Reporter synthetic genetic array Flow cytometry RNR3 promoter DNA damage response High-throughput screen Methyl methanesulfonate Differential EMAP Chemogenetic screen
2	Functional Genetic Analysis Reveals Intricate Roles of Conserved X-box Elements in Yeast Transcriptional Regulation Voll, Sarah 13 November 2013 (has links) Understanding the functional impact of physical interactions between proteins and DNA on gene expression is important for developing approaches to correct disease-associated gene dysregulation. I conducted a systematic, functional genetic analysis of protein-DNA interactions in the promoter region of the yeast ribonucleotide reductase subunit gene RNR3. I measured the transcriptional impact of systematically perturbing the major transcriptional regulator, Crt1, and three X-box sites on the DNA known to physically bind Crt1. This analysis revealed interactions between two of the three X-boxes in the presence of Crt1, and unexpectedly, a significant functional role of the X-boxes in the absence of Crt1. Further analysis revealed Crt1- independent regulators of RNR3 that were impacted by X-box perturbation. Taken together, these results support the notion that higher-order X-box-mediated interactions are important for RNR3 transcription, and that the X-boxes have unexpected roles in the regulation of RNR3 transcription that extend beyond their interaction with Crt1. functional genetic analysis transcription factor (TF) cis-regulatory element (CRE) binary interaction higher order interaction multiple linear regression additive multiplicative synthetic genetic array (SGA) green fluorescent protein (GFP) ribonucleotide reductase (RNR) yeast X-box transcriptional regulation RNR3
3	Functional Genetic Analysis Reveals Intricate Roles of Conserved X-box Elements in Yeast Transcriptional Regulation Voll, Sarah January 2013 (has links) Understanding the functional impact of physical interactions between proteins and DNA on gene expression is important for developing approaches to correct disease-associated gene dysregulation. I conducted a systematic, functional genetic analysis of protein-DNA interactions in the promoter region of the yeast ribonucleotide reductase subunit gene RNR3. I measured the transcriptional impact of systematically perturbing the major transcriptional regulator, Crt1, and three X-box sites on the DNA known to physically bind Crt1. This analysis revealed interactions between two of the three X-boxes in the presence of Crt1, and unexpectedly, a significant functional role of the X-boxes in the absence of Crt1. Further analysis revealed Crt1- independent regulators of RNR3 that were impacted by X-box perturbation. Taken together, these results support the notion that higher-order X-box-mediated interactions are important for RNR3 transcription, and that the X-boxes have unexpected roles in the regulation of RNR3 transcription that extend beyond their interaction with Crt1. functional genetic analysis transcription factor (TF) cis-regulatory element (CRE) binary interaction higher order interaction multiple linear regression additive multiplicative synthetic genetic array (SGA) green fluorescent protein (GFP) ribonucleotide reductase (RNR) yeast X-box transcriptional regulation RNR3

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