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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Identification and characterization of a human single-stranded telomeric DNA binding protein /

Szap, Matthew C., January 1997 (has links)
Thesis (Ph. D.)--Lehigh University, 1997. / Includes vita. Bibliography: leaves 136-150.
2

Classes of DNA associated with telomeres in the chironomids C. pallidivittatus and C. tentans

Kamnert, Iréne. January 1997 (has links)
Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.
3

Classes of DNA associated with telomeres in the chironomids C. pallidivittatus and C. tentans

Kamnert, Iréne. January 1997 (has links)
Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.
4

How Rif1 controls telomere length

Kedziora, Sylwia Maria January 2017 (has links)
The activation of replication origins is temporally regulated in S phase, with some origins activating early and some late. The molecular events controlling the temporal programme are not well understood, but in S. cerevisiae there is a close relationship between telomere length and nearby origin activation time. In the first part of this thesis I explore how the initiation time of origins near to telomeres is regulated by telomere length in a manner dependent on the Tel1 kinase. I demonstrate that an induced short telomere drives early activation of a nearby origin, but that in the absence of Tel1 the same origin activates late. In the second, major part of this thesis I focus on how the Rif1 protein negatively regulates length of the terminal TG1-3 repeats. While Rif1 has long been known to control telomere length, the mechanism through which Rif1 prevents telomere over-extension has remained unclear. Recently Rif1 was discovered to act in DNA replication control as a Protein Phosphatase 1-targeting subunit, directing Protein Phosphatase 1 (PP1) to dephosphorylate the MCM replicative helicase complex. I therefore investigated whether Rif1 also controls telomere length through PP1 interaction. I examine the effects of a mutant Rif1 with its PP1 interaction sites mutated to ablate PP1 binding. I found the mutant Rif1 binds normally to telomeres but causes a long telomere phenotype, similar to that in ∆rif1 cells, implicating Rif1-PP1 interaction in telomere length control. In further experiments I show that tethered PP1 can partially substitute for Rif1 in telomere length control. I also establish that the effect of Rif1-PP1 on telomere length does not operate indirectly through replication timing control, but rather appears to act through a direct pathway controlling telomerase recruitment. I discuss potential dephosphorylation targets, and the mechanism through which Rif1 and PP1 may control telomere length homeostasis. To summarise, my PhD research demonstrates that S. cerevisiae Rif1 acts with PP1 to repress telomerase-mediated TG1-3 repeat extension.
5

Investigating the role of the N-terminus of yeast telomerase reverse transcriptase in telomere maintenance

Ji, Hong, January 2007 (has links)
Thesis (Ph. D. in Biological Sciences)--Vanderbilt University, Dec. 2007. / Title from title screen. Includes bibliographical references.
6

A study of the composition and function of telomeric chromatin in drosophila melanogaster.

Doheny, James 05 1900 (has links)
The telomeres of most organisms are characterized by a protein-capping complex that protects chromosome ends, a series of repetitive subtelomeric sequences known as Telomere-Associated Sequences (TAS), and a behavioral phenomenon known as Telomere Position Effect (TPE). TPE is a phenomenon whereby normally active genes become repressed and silenced if relocated near to telomeres, and is thought to be a property of the proteins that constitute telomeric heterochromatin. Genetic dissection was used to exploit this phenomenon in order to identify components of telomeric heterochromatin in Drosophila melanogaster. Using genetic dissection, followed by a chromatin analysis technique known as Chromatin ImmunoPrecipitation (ChIP) I was able to identify three proteins, HDAC1, SU(VAR)3-9, and HP1c, as integral components of telomeric heterochromatin in Drosophila. HDAC1 and SU(VAR)3-9 are both believed to be involved in the gene-silencing process, and thus, their presence at telomeres could explain the phenomenon of TPE. Furthermore, I found that these proteins were specifically associated with the TAS region on the centromere-proximal side of the HeTA transposable elements that maintain telomere length in Drosophila. As a result of this, I proposed a model, which I call the ‘pairing-sliding model of telomere length control in Drosophila,’ which proposes that temporary incorrect pairing of Drosophila telomeres results in the deacetylation and subsequent methylation of the nucleosomes associated with the HeT-A and TART elements by TAS-associated HDAC1 and SU(VAR)3-9, resulting in these elements being transcriptionally silent. Thus, I propose that the TAS region, and the HDAC1 and SU(VAR)3-9 associated with it play a role in the negative regulation of telomere length in Drosophila.
7

Telomere dynamics and telomerase-independent cell survival in Arabidopsis thaliana

Watson, James M. 15 May 2009 (has links)
Telomeres are the nucleoprotein structures that protect the ends of eukaryotic chromosomes from being recognized as DNA double-strand breaks. Telomeres are recognized by the ribonucleoprotein telomerase, a reverse transcriptase that catalyzes addition of G-rich telomeric DNA repeats to the 3’ overhang of the telomere. The action of telomerase allows cells to overcome the end-replication problem defined by the inability of conventional DNA polymerases to fully replicate the end of the chromosome. Telomeric DNA tracts are maintained in a species-specific size range primarily through the competition between telomerase and the end-replication problem. In many organisms, recombinational activities can function at telomeres outside of the wild type range, in some cases resulting in telomerase-independent telomere maintenance. Telomere rapid deletion (TRD) can dramatically shorten elongated telomeres. Elongation of telomeres below the normal range in the absence of telomerase is known as alternative lengthening of telomeres (ALT). Here we demonstrate that telomeres in Arabidopsis thaliana are also subjected to these recombinational activities. Elongated telomeres in ku70 mutants are shortened by TRD. In contrast to other organisms, TRD functions on telomeres of wild type length. TRD produces extra-chromosomal telomeric circles, which can serve as substrates for ALT. In Arabidopsis, ALT may require the byproducts of TRD, as telomerase mutants with extremely short telomeres are unable to maintain telomeric repeats by recombination and instead secure their genome through an unknown mechanism. Finally, we follow the fate of cells with telomere-to-telomere fusions. Fusions are not propagated to viable progeny. We propose that a G1 checkpoint dependent upon the checkpoint protein ATM arrests cells following the break of a single telomere fusion. We design reporter constructs to follow the fate of individual cells with telomere fusions, and present initial characterization of their expression. We find no evidence for the propagation of telomere fusions in somatic cells, though later generation mutants will provide a better test of this hypothesis. This work begins the study of the fate of cells with telomere fusions in Arabidopsis. Furthermore, it sets the foundation for studying recombinational shortening and elongation of telomeres in Arabidopsis and the effects of these processes on telomere length regulation.
8

Telomeres and their associated factors in Arabidopsis thaliana

Idol, Rachel A 30 October 2006 (has links)
Telomeres are important protein-DNA structures at the ends of linear eukaryotic chromosomes that are necessary for genome integrity. Telomeres are maintained by intermittent action of telomerase. I explored the kinetics of telomere length homeostasis in the model plant Arabidopsis thaliana by crossing wild type plants to different generations of telomerase deficient plants, and then analyzing telomere length in the resulting progeny. Unexpectedly, I found plants lacking telomerase for seven generations can lengthen telomeres when telomerase is reintroduced, but one generation is not sufficient to reestablish the telomere set point. Est1 is a non-catalytic component of the Saccharomyces cerevisiae telomerase holoenzyme. To investigate the role of Est1 in higher eukaryotes, I identified two putative Est1 homologues in Arabidopsis, AtEST1a and AtEST1b. Plants deficient in AtEST1a displayed no vegetative or reproductive defects. However, plants deficient for AtEST1b were sterile and had severe vegetative and reproductive irregularities. Surprisingly, no defects in telomere maintenance were observed in any single or double mutant line. This suggests that the Est1- like proteins in plants have evolved new functions outside of telomere length maintenance and end protection.One consequence of telomere dysfunction is end-to-end chromosome fusion. In mammals, telomere fusion is mediated through NHEJ and requires DNA Ligase IV (Lig4). Lig4 is an essential component of the NHEJ pathway along with the Ku70/Ku80 heterodimer and DNA-PKcs. To address the mechanism of chromosome fusion in Arabidopsis, we investigated the role of Lig4 in mutant combinations lacking TERT, the catalytic subunit of telomerase, and Ku70. Surprisingly, telomere end-to-end fusions were observed in ku70 tert lig4 triple mutants, suggesting that neither Lig4 nor Ku70 are required for the fusion of critically shortened telomeres in Arabidopsis. To investigate the origin of genome instability, terminal restriction fragment analysis was performed on triple mutants. Strikingly, telomeres diminished five to six-fold faster than in a tert single mutant. Moreover, in the triple mutants, telomere tracts were extremely heterogeneous, suggesting that the telomeres were exposed to catastophic nucleolytic attack. These data provide the first evidence that Lig4 contributes to telomere maintenance and chromosome end protection.
9

A study of the composition and function of telomeric chromatin in drosophila melanogaster.

Doheny, James 05 1900 (has links)
The telomeres of most organisms are characterized by a protein-capping complex that protects chromosome ends, a series of repetitive subtelomeric sequences known as Telomere-Associated Sequences (TAS), and a behavioral phenomenon known as Telomere Position Effect (TPE). TPE is a phenomenon whereby normally active genes become repressed and silenced if relocated near to telomeres, and is thought to be a property of the proteins that constitute telomeric heterochromatin. Genetic dissection was used to exploit this phenomenon in order to identify components of telomeric heterochromatin in Drosophila melanogaster. Using genetic dissection, followed by a chromatin analysis technique known as Chromatin ImmunoPrecipitation (ChIP) I was able to identify three proteins, HDAC1, SU(VAR)3-9, and HP1c, as integral components of telomeric heterochromatin in Drosophila. HDAC1 and SU(VAR)3-9 are both believed to be involved in the gene-silencing process, and thus, their presence at telomeres could explain the phenomenon of TPE. Furthermore, I found that these proteins were specifically associated with the TAS region on the centromere-proximal side of the HeTA transposable elements that maintain telomere length in Drosophila. As a result of this, I proposed a model, which I call the ‘pairing-sliding model of telomere length control in Drosophila,’ which proposes that temporary incorrect pairing of Drosophila telomeres results in the deacetylation and subsequent methylation of the nucleosomes associated with the HeT-A and TART elements by TAS-associated HDAC1 and SU(VAR)3-9, resulting in these elements being transcriptionally silent. Thus, I propose that the TAS region, and the HDAC1 and SU(VAR)3-9 associated with it play a role in the negative regulation of telomere length in Drosophila.
10

A study of the composition and function of telomeric chromatin in drosophila melanogaster.

Doheny, James 05 1900 (has links)
The telomeres of most organisms are characterized by a protein-capping complex that protects chromosome ends, a series of repetitive subtelomeric sequences known as Telomere-Associated Sequences (TAS), and a behavioral phenomenon known as Telomere Position Effect (TPE). TPE is a phenomenon whereby normally active genes become repressed and silenced if relocated near to telomeres, and is thought to be a property of the proteins that constitute telomeric heterochromatin. Genetic dissection was used to exploit this phenomenon in order to identify components of telomeric heterochromatin in Drosophila melanogaster. Using genetic dissection, followed by a chromatin analysis technique known as Chromatin ImmunoPrecipitation (ChIP) I was able to identify three proteins, HDAC1, SU(VAR)3-9, and HP1c, as integral components of telomeric heterochromatin in Drosophila. HDAC1 and SU(VAR)3-9 are both believed to be involved in the gene-silencing process, and thus, their presence at telomeres could explain the phenomenon of TPE. Furthermore, I found that these proteins were specifically associated with the TAS region on the centromere-proximal side of the HeTA transposable elements that maintain telomere length in Drosophila. As a result of this, I proposed a model, which I call the ‘pairing-sliding model of telomere length control in Drosophila,’ which proposes that temporary incorrect pairing of Drosophila telomeres results in the deacetylation and subsequent methylation of the nucleosomes associated with the HeT-A and TART elements by TAS-associated HDAC1 and SU(VAR)3-9, resulting in these elements being transcriptionally silent. Thus, I propose that the TAS region, and the HDAC1 and SU(VAR)3-9 associated with it play a role in the negative regulation of telomere length in Drosophila. / Science, Faculty of / Zoology, Department of / Graduate

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