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Structural Mechanisms Of The Sliding Clamp And Sliding Clamp Loader: Insights Into Disease And Function: A Dissertation, Caroline M. Duffy Jul 2016

Structural Mechanisms Of The Sliding Clamp And Sliding Clamp Loader: Insights Into Disease And Function: A Dissertation, Caroline M. Duffy

GSBS Dissertations and Theses

Chromosomal replication is an essential process in all life. This dissertation highlights regulatory roles for two critical protein complexes at the heart of the replication fork: 1) the sliding clamp, the major polymerase processivity factor, and 2) the sliding clamp loader, a spiral-shaped AAA+ ATPase, which loads the clamp onto DNA.

The clamp is a promiscuous binding protein that interacts with at least 100 binding partners to orchestrate many processes on DNA, but spatiotemporal regulation of these binding interactions is unknown. Remarkably, a recent disease-causing mutant of the sliding clamp showed specific defects in DNA repair pathways. We aimed to ...


The Identification And Targeting Of Partially-Folded Conformations On The Folding Free-Energy Landscapes Of Als-Linked Proteins For Therapeutic Intervention: A Dissertation, Brian C. Mackness Apr 2016

The Identification And Targeting Of Partially-Folded Conformations On The Folding Free-Energy Landscapes Of Als-Linked Proteins For Therapeutic Intervention: A Dissertation, Brian C. Mackness

GSBS Dissertations and Theses

The hallmark feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), is the accumulation of cytoplasmic inclusions of key disease-linked proteins. Two of these proteins, TDP-43 and SOD1, represent a significant proportion of sporadic and familial ALS cases, respectively. The population of potentially aggregation-prone partially-folded states on the folding free-energy landscape may serve as a common mechanism for ALS pathogenesis. A detailed biophysical understanding of the folding and misfolding energy landscapes of TDP-43 and SOD1 can provide critical insights into the design of novel therapeutics to delay onset and progression in ALS.

Equilibrium unfolding studies on the RNA recognition ...


Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama Mar 2014

Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease is a fatal neurodegenerative disease. ALS is typically adult onset and is characterized by rapidly progressive loss of both upper and lower motor neurons that leads to death usually within 3-5 years. About 90% of all the cases are sporadic with no family history while the remaining 10% are familial cases with mutations in several genes including SOD1, FUS/TLS, TDP43 and C9ORF72.

FUS/TLS (Fused in Sarcoma/Translocated in Liposarcoma or FUS) is an RNA/DNA binding protein that is involved in multiple cellular functions including DNA damage ...


From Neurodegeneration To Infertility And Back - Exploring Functions Of Two Genes: Armc4 And Tardbp: A Dissertation, Wei Cheng Jan 2014

From Neurodegeneration To Infertility And Back - Exploring Functions Of Two Genes: Armc4 And Tardbp: A Dissertation, Wei Cheng

GSBS Dissertations and Theses

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset progressive neurodegenerative disease that causes degeneration in both upper and lower motor neurons. ALS progresses relentlessly after the onset of the disease, with most patients die within 3-5 years of diagnosis, largely due to respiratory failure. Since SOD1 became the first gene whose mutations were associated with ALS in 1993, more than 17 ALS causative genes have been identified. Among them, TAR DNA-binding protein (TARDBP) lies in the central of ALS pathology mechanism study, because TDP43 proteinopathy is observed not only in familial ALS cases carrying TARDBP mutations, but also in most of ...


Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan Jan 2012

Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan

GSBS Dissertations and Theses

Human papillomavirus infection is the cause of more than 99% of cervical cancer cases. The current vaccine is ineffective therapeutically; highlighting the need for continued papillomavirus research. One avenue that could be explored in this regard is the function of the papillomavirus E2 regulatory proteins. HPV E2 represses expression of the viral E6 and E7 oncoproteins. Reintroduction of E2 into cervical carcinoma cells results in growth arrest and cellular senescence. Understanding the mechanism of how E2 regulates the early promoter may be key to developing new therapeutic and prophylactic vaccines. Here, we describe regulation of E2 through acetylation and possibly ...


Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee Dec 2011

Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee

GSBS Dissertations and Theses

Tissue homeostasis in the adult Drosophila melanogaster intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation.

Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC ...


The Role Of Pc4 In Oxidative Stress: A Dissertation, Lijian Yu Jun 2011

The Role Of Pc4 In Oxidative Stress: A Dissertation, Lijian Yu

GSBS Dissertations and Theses

Oxidative stress is a cellular condition where cells are challenged by elevated levels of reactive oxygen species (ROS) that are produced endogenously or exogenously. ROS can damage vital cellular components, including lipid, protein, DNA and RNA. Oxidative damage to DNA often leads to cell death or mutagenesis, the underlying cause of various human disease states. Previously our laboratory discovered that human PC4 gene can prevent oxidative mutagenesis in the bacterium Escherichia coli and that the yeast homolog SUB1 has a conserved function in oxidation protection. In this thesis I examined the underlying mechanisms of PC4’s oxidation protection function. My ...


Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi Jun 2009

Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi

GSBS Dissertations and Theses

ARF, a potent tumor suppressor, positively regulates p53 by antagonizing MDM2, a negative regulator of p53, which in turn, results in either apoptosis or cell cycle arrest. ARF also suppresses the proliferation of cells lacking p53, and loss of ARF in p53-null mice, compared with ARF-null or p53-null mice, results in a broadened tumor spectrum and decreased tumor latency. This evidence suggests that ARF exerts both p53-dependent and p53-independent tumor suppressor activity. However, the molecular pathway and mechanism of ARF’s p53-independent tumor suppressor activity is not understood.

The antiapoptotic, metabolically regulated, transcriptional corepressor C-terminal binding protein 2 (CtBP2) has ...


Checkpoint Regulation Of Replication Forks In Response To Dna Damage: A Dissertation, Nicholas Adrian Willis May 2009

Checkpoint Regulation Of Replication Forks In Response To Dna Damage: A Dissertation, Nicholas Adrian Willis

GSBS Dissertations and Theses

Faithful duplication and segregation of undamaged DNA is critical to the survival of all organisms and prevention of oncogenesis in multicellular organisms. To ensure inheritance of intact DNA, cells rely on checkpoints. Checkpoints alter cellular processes in the presence of DNA damage preventing cell cycle transitions until replication is completed or DNA damage is repaired.

Several checkpoints are specific to S-phase. The S-M replication checkpoint prevents mitosis in the presence of unreplicated DNA. Rather than outright halting replication, the S-phase DNA damage checkpoint slows replication in response to DNA damage. This checkpoint utilizes two general mechanisms to slow replication. First ...


Functional Interaction Of Bpv-1 E2 With The Papillomavirus Genome: A Dissertation, Suzanne Marie Melanson Feb 2009

Functional Interaction Of Bpv-1 E2 With The Papillomavirus Genome: A Dissertation, Suzanne Marie Melanson

GSBS Dissertations and Theses

The bovine papillomavirus type 1 E2 protein is a multifunctional early viral protein with roles in all phases of the cell cycle. E2 is required during G1 as a transcription factor, in S phase to initiate viral replication and during mitosis to tether the viral genome to dividing DNA. The viral genome contains 17 E2 binding sites, the majority of which are concentrated in the long control region (LCR), a regulatory region that is upstream of the viral coding sequence. The role of these binding sites has been explored in vitro using small plasmids and E1 and E2 proteins expressed ...


Regulation Of Reactive Nitrogen Species (Rns) Metabolism And Resistance Mechanisms In Haemophilus Influenzae: A Dissertation, Jane Colleen Harrington Nov 2008

Regulation Of Reactive Nitrogen Species (Rns) Metabolism And Resistance Mechanisms In Haemophilus Influenzae: A Dissertation, Jane Colleen Harrington

GSBS Dissertations and Theses

Haemophilus influenzae encounters niches within the human host that are predicted to differ in availability of oxygen and reactive nitrogen species (RNS: nitrite and nitric oxide), which influence the environmental redox state. Previously reported data has indicated that an altered redox condition could serve as a signal recognized by H. influenzae to optimize its survival within host microenvironments. To elucidate the role of redox signaling in virulence, we examined regulation by the FNR homolog of H. influenzae, whose counterpart in E. coli has been reported to be a direct oxygen sensor and a regulator of genes responsible for RNS metabolism ...


Epigenetic Telomere Protection By Drosophila Dna Damage Response Pathways: A Dissertation, Sarah R. Oikemus Sep 2006

Epigenetic Telomere Protection By Drosophila Dna Damage Response Pathways: A Dissertation, Sarah R. Oikemus

GSBS Dissertations and Theses

Several aspects of Drosophila telomere biology indicate that telomere protection can be regulated by an epigenetic mechanism. First, terminally deleted chromosomes can be stably inherited and do not induce damage responses such as apoptosis or cell cycle arrest. Second, the telomere protection proteins HP1 and HOAP localize normally to these chromosomes and protect them from fusions. Third, unprotected telomeres still contain HeT-A sequences at sites of fusions. Taken together these observations support a model in which an epigenetic mechanism mediated by DNA damage response proteins protects Drosophilatelomeres from fusion.

Work presented in this thesis demonstrates that the Drosophila proteins ...


Plagl2 Cooperates In Leukemia Development By Upregulating Mpl Expression: A Dissertation, Sean F. Landrette Jun 2006

Plagl2 Cooperates In Leukemia Development By Upregulating Mpl Expression: A Dissertation, Sean F. Landrette

GSBS Dissertations and Theses

Chromosomal alterations involving the RUNXI or CBFB genes are specifically and recurrently associated with human acute myeloid leukemia (AML). One such chromosomal alteration, a pericentric inversion of chromosome 16, is present in the majority of cases of the AML subtype M4Eo. This inversion joins CBFB with the smooth muscle myosin gene MYH11 creating the fusion CBFB-MYH11. Knock-in studies in the mouse have demonstrated that expression of the protein product of the Cbfb-MYH11fusion, Cbfβ-SMMHC, predisposes mice to AML and that chemical mutagenesis both accelerates and increases the penetrance of the disease (Castilla et al., 1999). However, the mechanism of transformation ...


Human Rad51: Regulation Of Cellular Localization And Function In Response To Dna Damage: A Dissertation, Brian Thomas Bennett Feb 2006

Human Rad51: Regulation Of Cellular Localization And Function In Response To Dna Damage: A Dissertation, Brian Thomas Bennett

GSBS Dissertations and Theses

Repair of DNA double-strand breaks via homologous recombination is an essential pathway for vertebrate cell development and maintenance of genome integrity throughout the organism’s lifetime. The Rad51 enzyme provides the central catalytic function of homologous recombination while many other proteins are involved in regulation and assistance of Rad51 activity, including a group of five proteins referred to as Rad51 paralogs (Rad51B, Rad51C, Rad51D, Xrcc2, Xrcc3). At the start of my work, cellular studies of human Rad51 (HsRad51) had shown only that it forms distinct nuclear foci in response to DNA damage. Additionally, no information regarding the cellular localization, potential ...


Regulation Of Cell Growth And Differentiation Within The Context Of Nuclear Architecture By The Runx2 Transcription Factor: A Dissertation, Daniel W. Young Sep 2005

Regulation Of Cell Growth And Differentiation Within The Context Of Nuclear Architecture By The Runx2 Transcription Factor: A Dissertation, Daniel W. Young

GSBS Dissertations and Theses

The Runx family of transcription factors performs an essential role in animal development by controlling gene expression programs that mediate cell proliferation, growth and differentiation. The work described in this thesis is concerned with understanding mechanisms by which Runx proteins support this program of gene expression within the architectural context of the mammalian cell nucleus. Multiple aspects of nuclear architecture are influenced by Runx2 proteins including sequence-specific DNA binding at gene regulatory regions, organization of promoter chromatin structure, and higher-order compartmentalization of proteins in nuclear foci. This work provides evidence for several functional activities of Runx2 in relation to architectural ...


Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop Jul 2005

Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop

GSBS Dissertations and Theses

The prevalence of diabetes is approaching epidemic proportions worldwide. There is currently no cure for type 1 diabetes, and successful treatment requires constant monitoring of blood sugars and use of exogenous insulin to prevent hyperglycemia. Diabetes will be curable when pancreatic β-islet cells can be transplanted into diabetes patients without requiring long-term immunosuppression. This will require learning more about the induction of functional tolerance, a state that maintains the competence of the immune system to most antigens but protects graft-specific antigens from immune rejection, permitting transplantation. One known mechanism of peripheral tolerance is T cell anergy, a phenotype of hypo-reponsiveness ...


Regulation And Function Of Runx2 During Chondrogenic And Osteogenic Differentiation: A Dissertation, Christopher J. Lengner Dec 2004

Regulation And Function Of Runx2 During Chondrogenic And Osteogenic Differentiation: A Dissertation, Christopher J. Lengner

GSBS Dissertations and Theses

Members of the Runx family of transcription factors play essential roles in the differentiation and development of several organ systems. Here we address the contribution of the osteoblast-related Runx gene, Runx2, to the osteogenic and chondrogenic differentiation of mesenchymal stem cells. Using a transgenic mouse model, we observe Runx2 transcription through one of its two known promoters (designated P1 in pre-cartilaginous mesenchymal condensations as early as E9.5. Runx2 gene activity is later repressed at the onset of cartilage formation, both in vivo and in vitro, necessitating examination of the regulation and function of Runx2 in mesenchymal stem cells. We ...


The Roles Of Dna Mismatch Repair And Recombination In Drug Resistance: A Dissertation, Melissa A. Calmann Dec 2004

The Roles Of Dna Mismatch Repair And Recombination In Drug Resistance: A Dissertation, Melissa A. Calmann

GSBS Dissertations and Theses

Cells have evolved different pathways in order to tolerate damage produced by different cytotoxic agents. Each agent reacts differently with DNA causing formation of different types of adducts, each eliciting the SOS stress response to induce different cellular repair pathways. One such type of substrate generated by cytotoxic agents is the DNA double strand break (DSB). The main pathway to repair such damage in the cell is through a process of recombination. In this thesis, I specifically examined the anti-cancer therapeutic agent cisplatin, which forms single- and double-strand breaks in DNA, and methylating agents, which are proposed to also be ...


Functional And Structural Analysis Of The Yeast Swi/Snf Complex: A Dissertation, Corey Lewis Smith Jul 2004

Functional And Structural Analysis Of The Yeast Swi/Snf Complex: A Dissertation, Corey Lewis Smith

GSBS Dissertations and Theses

Modulating chromatin structure is an important step in maintaining control over the eukaryotic genome. SWI/SNF, one of the complexes belonging to the growing family of ATP-dependent chromatin remodeling enzymes, is involved in controlling the expression of a number of inducible genes whose proper regulation is vital for metabolism and progression through mitosis. The mechanism by which SWI/SNF modulates chromatin structure at the nucleosome level is an important aspect of this regulation. The work in this dissertation focuses on how the Saccharomyces cerevisiae SWI/SNF complex uses the energy of ATP-hydrolysis to alter DNA-histone contacts in nucleosomes. This has ...


Homologous Recombinational Dna Repair: From Prokaryotes To Eukaryotes: A Dissertation, Anthony L. Forget Apr 2004

Homologous Recombinational Dna Repair: From Prokaryotes To Eukaryotes: A Dissertation, Anthony L. Forget

GSBS Dissertations and Theses

The error free repair of DNA double strand breaks through the homologous recombinational repair pathway is essential for organisms of all types to sustain life. A detailed structural and mechanistic understanding of this pathway has been the target of intense study since the identification of bacterial recA, the gene whose product is responsible for the catalysis of DNA strand exchange, in 1965. The work presented here began with defining residues that are important for the assembly and stability of the RecA filament, and progressed to the identification of residues critical for the transfer of ATP-mediated allosteric information between subunits in ...


The Structural Basis For The Phosphorylation-Induced Activation Of Smad Proteins: A Dissertation, Benoy M. Chacko Feb 2004

The Structural Basis For The Phosphorylation-Induced Activation Of Smad Proteins: A Dissertation, Benoy M. Chacko

GSBS Dissertations and Theses

The Smad proteins transduce the signal of transforming growth factor-β (TGF-β) and related factors from the cell surface to the nucleus. Following C-terminal phosphorylation by a corresponding receptor kinase, the R-Smad proteins form heteromeric complexes with Smad4. These complexes translocate into the nucleus, bind specific transcriptional activators and DNA, ultimately modulating gene expression. Though studied through a variety of means, the stoichiometry of the R-Smad/Smad4 complex is unclear. We investigated the stoichiometry of the phosphorylation-induced R-Smad/Smad4 complex by using acidic amino acid substitutions to simulate phosphorylation. Size exclusion chromatography, analytical ultracentrifugation, and isothermal titration calorimetry analysis revealed that ...


Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil Jan 2004

Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil

GSBS Dissertations and Theses

Activation of the basic helix-loop-helix (bHLH) gene TAL1 is the most common genetic event seen in both childhood and adult T cell acute lymphoblastic leukemia (T-ALL). Despite recent success in treating T-ALL patients, TAL1 patients do not respond well to current therapies. In hopes of leading the way to better therapies for these patients, we have sought to determine the mechanism(s) of Tal1 induced leukemia in mice. By generating a DNA-binding mutant Tal1 transgenic mouse we have determined that the DNA binding activity of Tal1 is not required to induce leukemia. We have also shown that Tal1 expression in ...


Function Of The Zinc-Finger Repressor Nlz In The Developing Zebrafish Hindbrain: A Dissertation, Alexander Peter Runko Oct 2003

Function Of The Zinc-Finger Repressor Nlz In The Developing Zebrafish Hindbrain: A Dissertation, Alexander Peter Runko

GSBS Dissertations and Theses

Generation of the primitive neuroectoderm into specialized brain subdivisions, such as the hindbrain primordium, involves the regulated coordination of complex morphogenetic and molecular mechanisms. These processes are evident in the segregation of the zebrafish hindbrain into seven distinct lineage-restricted compartments, termed rhombomeres (r), which are established by the interplay of several spatially-restricted expressed genes. These include transcription factors, members of specific signaling pathways and specialized molecules that mediate cell adhesion and identity. Despite their extensive characterization, it is evident that other genes are involved to mediate the proper specification and segregation of individual rhombomeres. One candidate that likely fits this ...


Intranuclear Trafficking Of Runx/Aml/Cbfa/Pebp2 Transcription Factors In Living Cells: A Dissertation, Kimberly Stacy Harrington Mar 2003

Intranuclear Trafficking Of Runx/Aml/Cbfa/Pebp2 Transcription Factors In Living Cells: A Dissertation, Kimberly Stacy Harrington

GSBS Dissertations and Theses

The family of runt related transcription factors (RUNX/Cbfa/AML/PEBP2) are essential for cellular differentiation and fetal development. RUNX factors are distributed throughout the nucleus in punctate foci that are associated with the nuclear matrix/scaffold and generally correspond with sites of active transcription. Truncations of RUNX proteins that eliminate the C-terminus including a 31-amino acid segment designated the nuclear matrix targeting signal (NMTS) lose nuclear matrix association and result in lethal hematopoietic (RUNX1) and skeletal (RUNX2) phenotypes in mice. These findings suggest that the targeting of RUNX factors to subnuclear foci may mediate the formation of multimeric regulatory ...


The Role Of The Swi/Snf Component Ini1 In Mammalian Development And Tumorigenesis: A Dissertation, Cynthia J. Guidi Feb 2003

The Role Of The Swi/Snf Component Ini1 In Mammalian Development And Tumorigenesis: A Dissertation, Cynthia J. Guidi

GSBS Dissertations and Theses

In vivo DNA is compacted tightly, via its association with histones and non-histone proteins, into higher-order chromatin structure. In this state, the DNA is refractory to the cellular factors that require access to DNA. The repressive nature of chromatin is alleviated in part by the action enzymes that modify chromatin structure. There are two major groups of chromatin modifying enzymes: those that post-translationally modify histones by the addition of small chemical moieties and those that utilize the energy derived from ATP hydrolysis to physically disrupt chromatin structure. The SWI/SNF enzyme belongs to this latter group.

The SWI/SNF complex ...


The Human Rad52 Protein: A Correlation Of Protein Function With Oligomeric State: A Dissertation, Janice A. Lloyd Sep 2002

The Human Rad52 Protein: A Correlation Of Protein Function With Oligomeric State: A Dissertation, Janice A. Lloyd

GSBS Dissertations and Theses

The regulation of protein function through oligomerization is a common theme in biological systems. In this work, I have focused on the effects of the oligomeric states of the human Rad52 protein on activities related to DNA binding. HsRad52, a member of the RAD52 epistasis group, is thought to play an important and as yet undefined role in homologous recombination. HsRad52 preferentially binds to ssDNA over dsDNA and stimulates HsRad51-mediated strand exchange (Benson et al., 1998). In either the presence or absence of DNA, HsRad52 has been observed to form both 10 nm ring-like structures as well as higher ...


Allosteric Regulation Of Recombination Enzymes E. Coli Reca And Human Rad51: A Dissertation, Julie Kelley De Zutter Aug 2000

Allosteric Regulation Of Recombination Enzymes E. Coli Reca And Human Rad51: A Dissertation, Julie Kelley De Zutter

GSBS Dissertations and Theses

ATP plays a critical role in the regulation of many enzyme processes. In this work, I have focused on the ATP mediated regulation of the recombination processes catalyzed by the E. coliRecA and the human Rad51 proteins. The RecA protein is a multifunctional enzyme, which plays a central role in the processes of recombinational DNA repair, homologous genetic recombination and in the activation of the cellular SOS response to DNA damage. Each of these functions requires a common activating step, which is the formation of a RecA-ATP-ssDNA nucleoprotein filament. The binding of ATP results in the induction of a ...


Transcriptional Regulation By The Saccharomyces Cerevisiae Centromere-Binding Protein Cp1: A Dissertation, Kevin F. O'Connell Jun 1994

Transcriptional Regulation By The Saccharomyces Cerevisiae Centromere-Binding Protein Cp1: A Dissertation, Kevin F. O'Connell

GSBS Dissertations and Theses

CP1 (encoded by the gene CEP1) is a sequence-specific DNA-binding protein of Saccharomyces cerevisiae that recognizes a sequence element (CDEI) found in both yeast centromeres and gene promoters. Strains lacking CP1 are viable but exhibit defects in growth, chromosome segregation, and methionine biosynthesis. To investigate the basis of the methionine requirement, a YEp24-based yeast genomic DNA library was screened for plasmids which suppressed the methionine auxotrophy of a cep1 null mutant. The suppressing plasmids contained either CEP1 or DNA derived from the PHO4 locus. PHO4 encodes a factor which positively regulates transcription of genes involved in phosphate metabolism via an ...


Genetic Analysis Of The Saccharomyces Cerevisiae Centromere-Binding Protein Cp1: A Thesis, Daniel C. Masison Mar 1993

Genetic Analysis Of The Saccharomyces Cerevisiae Centromere-Binding Protein Cp1: A Thesis, Daniel C. Masison

GSBS Dissertations and Theses

CP1 is a sequence specific DNA-binding protein of the yeast Saccharomyces cerevisiae which recognizes the highly conserved centromere DNA element I (CDEI) of yeast centromeres. The gene encoding CP1, which was designated CEP1 for centromere protein 1, was cloned and sequenced. CEP1 encodes a highly acidic protein of molecular weight 39,400. CEP1 was mapped to a position 4.6 centiMorgans centromere distal to SUP4 on the right arm of chromosome X. Phenotypic analysis of cep1 mutants demonstrated that yeast strains lacking CP1 are viable but have a 35% increase in cell doubling time, a ninefold increase in the rate ...