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Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this, telomerase uses a small section of its integral RNA subunit (TR) to reiteratively copy a short, canonically 6-nt, sequence repeatedly in a processive manner using

Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this, telomerase uses a small section of its integral RNA subunit (TR) to reiteratively copy a short, canonically 6-nt, sequence repeatedly in a processive manner using a complex and currently poorly understood mechanism of template translocation to stop nucleotide addition, regenerate its template, and then synthesize a new repeat. In this study, several novel interactions between the telomerase protein and RNA components along with the DNA substrate are identified and characterized which come together to allow active telomerase repeat addition. First, this study shows that the sequence of the RNA/DNA duplex holds a unique, single nucleotide signal which pauses DNA synthesis at the end of the canonical template sequence. Further characterization of this sequence dependent pause signal reveals that the template sequence alone can produce telomerase products with the characteristic 6-nt pattern, but also works cooperatively with another RNA structural element for proper template boundary definition. Finally, mutational analysis is used on several regions of the protein and RNA components of telomerase to identify crucial determinates of telomerase assembly and processive repeat synthesis. Together, these results shed new light on how telomerase coordinates its complex catalytic cycle.
ContributorsBrown, Andrew F (Author) / Chen, Julian J. L. (Thesis advisor) / Jones, Anne (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
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The communication of genetic material with biomolecules has been a major interest in cancer biology research for decades. Among its different levels of involvement, DNA is known to be a target of several antitumor agents. Additionally, tissue specific interaction between macromolecules such as proteins and structurally important regions of DNA

The communication of genetic material with biomolecules has been a major interest in cancer biology research for decades. Among its different levels of involvement, DNA is known to be a target of several antitumor agents. Additionally, tissue specific interaction between macromolecules such as proteins and structurally important regions of DNA has been reported to define the onset of certain types of cancers.

Illustrated in Chapter 1 is the general history of research on the interaction of DNA and anticancer drugs, most importantly different congener of bleomycin (BLM). Additionally, several synthetic analogues of bleomycin, including the structural components and functionalities, are discussed.

Chapter 2 describes a new approach to study the double-strand DNA lesion caused by antitumor drug bleomycin. The hairpin DNA library used in this study displays numerous cleavage sites demonstrating the versatility of bleomycin interaction with DNA. Interestingly, some of those cleavage sites suggest a novel mechanism of bleomycin interaction, which has not been reported before.

Cytidine methylation has generally been found to decrease site-specific cleavage of DNA by BLM, possibly due to structural change and subsequent reduced bleomycin-mediated recognition of DNA. As illustrated in Chapter 3, three hairpin DNAs known to be strongly bound by bleomycin, and their methylated counterparts, were used to study the dynamics of bleomycin-induced degradation of DNAs in cancer cells. Interestingly, cytidine methylation on one of the DNAs has also shown a major shift in the intensity of bleomycin induced double-strand DNA cleavage pattern, which is known to be a more potent form of bleomycin induced cleavages.

DNA secondary structures are known to play important roles in gene regulation. Chapter 4 demonstrates a structural change of the BCL2 promoter element as a result of its dynamic interaction with the individual domains of hnRNP LL, which is essential to facilitate the transcription of BCL2. Furthermore, an in vitro protein synthesis technique has been employed to study the dynamic interaction between protein domains and the i-motif DNA within the promoter element. Several constructs were made involving replacement of a single amino acid with a fluorescent analogue, and these were used to study FRET between domain 1 and the i-motif, the later of which harbored a fluorescent acceptor nucleotide analogue.
ContributorsRoy, Basab (Author) / Hecht, Sidney M. (Thesis advisor) / Jones, Anne (Committee member) / Levitus, Marcia (Committee member) / Chaput, John (Committee member) / Arizona State University (Publisher)
Created2014
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The honors thesis presented in this document describes an extension to an electrical engineering capstone project whose scope is to develop the receiver electronics for an RF interrogator. The RF interrogator functions by detecting the change in resonant frequency of (i.e, frequency of maximum backscatter from) a target resulting

The honors thesis presented in this document describes an extension to an electrical engineering capstone project whose scope is to develop the receiver electronics for an RF interrogator. The RF interrogator functions by detecting the change in resonant frequency of (i.e, frequency of maximum backscatter from) a target resulting from an environmental input. The general idea of this honors project was to design three frequency selective surfaces that would act as surrogate backscattering or reflecting targets that each contains a distinct frequency response. Using 3-D electromagnetic simulation software, three surrogate targets exhibiting bandpass frequency responses at distinct frequencies were designed and presented in this thesis.

ContributorsSisk, Ryan Derek (Author) / Aberle, James (Thesis director) / Chakraborty, Partha (Committee member) / Electrical Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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In February 1953, Linus Pauling and Robert Brainard Corey, two scientists working at the California Institute of Technology in Pasadena, California, proposed a structure for deoxyribonucleic acid, or DNA, in their article “A Proposed Structure for the Nucleic Acids,” henceforth “Nucleic Acids.” In the article, Pauling and Corey suggest a

In February 1953, Linus Pauling and Robert Brainard Corey, two scientists working at the California Institute of Technology in Pasadena, California, proposed a structure for deoxyribonucleic acid, or DNA, in their article “A Proposed Structure for the Nucleic Acids,” henceforth “Nucleic Acids.” In the article, Pauling and Corey suggest a model for nucleic acids, including DNA, that consisted of three nucleic acid strands wound together in a triple helix. “Nucleic Acids” was published in Proceedings of the National Academy of Sciences shortly after scientists came to the consensus that genes, the biological factors that control how organisms develop, contained DNA. Though scientists proved Pauling and Corey’s model incorrect, “Nucleic Acids” helped scientists understand DNA’s structure and function as genetic material.

Created2019-08-26
Description

In April 1953, James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure of Deoxyribose Nucleic Acid” or “A Structure for Deoxyribose Nucleic Acid,” in the journal Nature. In the article, Watson and Crick propose a novel structure for deoxyribonucleic acid or DNA. In 1944, Oswald T.

In April 1953, James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure of Deoxyribose Nucleic Acid” or “A Structure for Deoxyribose Nucleic Acid,” in the journal Nature. In the article, Watson and Crick propose a novel structure for deoxyribonucleic acid or DNA. In 1944, Oswald T. Avery and his group at Rockefeller University in New York City, New York published experimental evidence that DNA contained genes, the biological factors called genes that dictate how organisms grow and develop. Scientists did not know how DNA’s function led to the passage of genetic information from cell to cell, or organism to organism. The model that Watson and Crick presented connected the concept of genes to heredity, growth, and development. As of 2018, most scientists accept Watson and Crick’s model of DNA presented in the article. For their work on DNA, Watson and Crick shared the 1962 Nobel Prize in Physiology or Medicine with Maurice Wilkins.

Created2019-10-31
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In 1956, Gunther Stent, a scientist at the University of California Berkeley in Berkeley, California, coined the terms conservative, semi-conservative, and dispersive to categorize the prevailing theories about how DNA replicated. Stent presented a paper with Max Delbrück titled “On the Mechanism of DNA Replication” at the McCollum-Pratt Symposium at

In 1956, Gunther Stent, a scientist at the University of California Berkeley in Berkeley, California, coined the terms conservative, semi-conservative, and dispersive to categorize the prevailing theories about how DNA replicated. Stent presented a paper with Max Delbrück titled “On the Mechanism of DNA Replication” at the McCollum-Pratt Symposium at Johns Hopkins University in Baltimore, Maryland. In response to James Watson and Francis Crick’s proposed structure of DNA in 1953, scientists debated how DNA replicated. Throughout the debate, scientists hypothesized different theories about how DNA replicated, but none of the theories had sound experimental data. Stent introduced DNA replication classes that, if present in DNA, would yield distinct experimental results. Conservative, semi-conservative, and dispersive DNA replication categories shaped scientists' research into how DNA replicated, which led to the conclusion that DNA replicated semi-conservatively.

Created2019-10-31
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William Thomas Astbury studied the structures of fibrous materials, including fabrics, proteins, and deoxyribonucleic acid, or DNA, in England during the twentieth century. Astbury employed X-ray crystallography, a technique in which scientists use X-rays to learn about the molecular structures of materials. Astbury worked at a time when scientists had

William Thomas Astbury studied the structures of fibrous materials, including fabrics, proteins, and deoxyribonucleic acid, or DNA, in England during the twentieth century. Astbury employed X-ray crystallography, a technique in which scientists use X-rays to learn about the molecular structures of materials. Astbury worked at a time when scientists had not yet identified DNA’s structure or function in genes, the genetic components responsible for how organisms develop and reproduce. He was one of the first scientists to use X-ray crystallography to study the structure of DNA. According to historians, Astbury helped establish the field of molecular biology as he connected microscopic changes in the structure of materials to changes in their large-scale properties. Astbury and his images helped scientists to understand the structure of DNA and its role in genetics.

Created2019-06-03
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In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes, or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. The article is titled “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction

In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes, or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. The article is titled “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III,” hereafter “Transformation.” The authors isolated, purified, and characterized genes within bacteria and found evidence that those genes were made of DNA and not protein. Though scientists were initially skeptical that genes were made of DNA, they later recognized that the data reported in “Transformation” were clear evidence that DNA was genetic material, a revelation that furthered research about how organisms grow, develop, and pass on traits to offspring.

Created2019-07-08
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In 1951 and 1952, Alfred Hershey and Martha Chase conducted a series of experiments at the Carnegie Institute of Washington in Cold Spring Harbor, New York, that verified genes were made of deoxyribonucleic acid, or DNA. Hershey and Chase performed their experiments, later named the Hershey-Chase experiments, on viruses that

In 1951 and 1952, Alfred Hershey and Martha Chase conducted a series of experiments at the Carnegie Institute of Washington in Cold Spring Harbor, New York, that verified genes were made of deoxyribonucleic acid, or DNA. Hershey and Chase performed their experiments, later named the Hershey-Chase experiments, on viruses that infect bacteria, also called bacteriophages. The experiments followed decades of scientists’ skepticism about whether genetic material was composed of protein or DNA. The most well-known Hershey-Chase experiment, called the Waring Blender experiment, provided concrete evidence that genes were made of DNA. The Hershey-Chase experiments settled the long-standing debate about the composition of genes, thereby allowing scientists to investigate the molecular mechanisms by which genes function in organisms.

Created2019-06-23
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In April 1953, Rosalind Franklin and Raymond Gosling, published “Molecular Configuration in Sodium Thymonucleate,” in the scientific journal Nature. The article contained Franklin and Gosling’s analysis of their X-ray diffraction pattern of thymonucleate or deoxyribonucleic acid, known as DNA. In the early 1950s, scientists confirmed that genes, the heritable factors

In April 1953, Rosalind Franklin and Raymond Gosling, published “Molecular Configuration in Sodium Thymonucleate,” in the scientific journal Nature. The article contained Franklin and Gosling’s analysis of their X-ray diffraction pattern of thymonucleate or deoxyribonucleic acid, known as DNA. In the early 1950s, scientists confirmed that genes, the heritable factors that control how organisms develop, contained DNA. However, at the time scientists had not determined how DNA functioned or its three-dimensional structure. In their 1953 paper, Franklin and Gosling interpret X-ray diffraction patterns of DNA fibers that they collected, which show the scattering of X-rays from the fibers. The patterns provided information about the three-dimensional structure of the molecule. “Molecular Configuration in Sodium Thymonucleate” shows the progress Franklin and Gosling made toward understanding the three-dimensional structure of DNA.

Created2019-11-30