Дисертації з теми "Telomere DNA"
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Moye, Aaron Lavel. "Understanding the relationship between telomeres, telomerase, and DNA G-quadruplexes." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17713.
Повний текст джерелаKamnert, Iréne. "Classes of DNA associated with telomeres in the chironomids C. pallidivittatus and C. tentans." Lund : Dept. of Genetics, Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/39009480.html.
Повний текст джерелаXing, Xuekun. "DNA replication and telomere resolution in vaccinia virus." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq23557.pdf.
Повний текст джерелаOjani, Maryam. "Relationship between DNA damage response and telomere maintenance." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/7441.
Повний текст джерелаCarlos, A. R. "DNA damage responses to loss of telomere integrity." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:27bcf3b6-edb9-47e2-af7c-c7ba9b431572.
Повний текст джерелаCabuy, Erik. "Investigations of telomere maintenance in DNA damage response defective cells and telomerase in brain tumours." Thesis, Brunel University, 2005. http://bura.brunel.ac.uk/handle/2438/5157.
Повний текст джерелаXu, Mengyuan. "The Role of Shelterin Proteins in Telomere DNA Protection and Regulation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1585760345643995.
Повний текст джерелаBrown, Karen E. "Telomere-directed breakage of the human Y chromosome." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260731.
Повний текст джерелаDenham, Elizabeth. "The Effects of Relocating the Ku-binding Stem-loop of Telomerase RNA on Telomere Healing Events." Thesis, Boston College, 2008. http://hdl.handle.net/2345/528.
Повний текст джерелаThesis advisor: Clare O'Connor
In most eukaryotes, the enzyme telomerase adds telomeric DNA repeats to the 3' ends of chromosomes in order to stabilize them and protect them from degradation. In the budding yeast Saccharomyces cerevisiae, telomerase is a ribonucleoprotein complex consisting of multiple protein subunits and an approximately 1.3 kb RNA component termed TLC1. Among the various proteins involved in telomerase, Ku is a heterodimer that binds both to double-stranded DNA and to a 48 nucleotide stem loop on the TLC1 RNA. Beyond its function of extending telomeres at the ends of chromosomes, telomerase can also be instrumental in repairing double-stranded DNA breaks (DSBs) by adding telomeric repeats at the site of the break. This stabilizes the damaged chromosome, but also silences genes proximal to the break. Ku is an important factor in the recruitment of telomerase to these double stranded breaks, so this investigation explored whether TLC1 structural variants with relocated Ku-binding sites are still capable of healing chromosomes via the addition of telomeres. It was determined that the TLC1 RNA is flexible and can retain its function with relocated and additional Ku-binding stem loops
Thesis (BS) — Boston College, 2008
Submitted to: Boston College. College of Arts and Sciences
Discipline: Biology
Discipline: College Honors Program
Tuntiwechapikul, Wirote. "Studies of a G-quadruplex-specific cleaving reagent, expansion of long repetitive DNA sequences, and a cytosine-specific alkylating aza-enediyne /." Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3055255.
Повний текст джерелаYasaei, Hemad. "Analysis of telomere maintenance in artemis defective human cell lines." Thesis, Brunel University, 2009. http://bura.brunel.ac.uk/handle/2438/4406.
Повний текст джерелаEbrahimi, Hani. "The effect of DNA replication on telomere positioning in S. cerevisiae." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26454.
Повний текст джерелаCastillejo-López, Casimiro. "Repetitive DNA in search of a function a study of telomeric and centromeric sequences in Chironomus /." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/68945096.html.
Повний текст джерелаBallal, Rahul. "BRCA1 localization to the telomere and its loss upon DNA damage." Connect to Electronic Thesis (CONTENTdm), 2010. http://worldcat.org/oclc/642695417/viewonline.
Повний текст джерелаDenham, Joshua. "Telomere, DNA Methylation and Gene Expression changes caused by exercise training." Thesis, Federation University Australia, 2016. http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/99858.
Повний текст джерелаDoctor of Philosophy
Oikemus, Sarah R. "Epigenetic Telomere Protection by Drosophila DNA Damage Response Pathways: A Dissertation." eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/229.
Повний текст джерелаPedroso, Ilene Marie. "The Outer Limits: Telomere Maintenance by TRF2 and G-Quadruplex DNA Structures." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/24.
Повний текст джерелаMartinez, Alaina R. "Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1479924417740462.
Повний текст джерелаMéndez-Bermúdez, Aarón. "Telomere stability in cancer cells and the role of DNA mismatch repair." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/30378.
Повний текст джерелаRoberts, Jennifer Nicole. "Investigating the DNA binding properties of the Telomere End-Binding Protein Cdc13." Connect to online resource, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3337145.
Повний текст джерелаSmiraldo, Phillip G. "The Rad51d DNA Repair Gene is Required for Chromosome and Telomore Stability in Mammalian Cells." University of Toledo Health Science Campus / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=mco1146675938.
Повний текст джерелаLangston, Rachel Elizabeth, and Rachel Elizabeth Langston. "DNA Replication Defects in the Telomere Induce Chromosome Instability in a Single Cell Cycle." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/622910.
Повний текст джерелаSantos, Gabriel Arantes Galvão Dias dos. "Caracterização molecular da atividade de interação da proteína RPA-1 com os telômeros de Leishmania spp." Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/153962.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Entre as espécies do gênero Leishmania estão os protozoários que causam leishmaniose, uma doença tropical negligenciada endêmica em muitos países, incluindo o Brasil. Métodos de controle e tratamento ainda são ineficientes e a resistência a drogas é um desafio. Por isso, pesquisas para entender melhor a biologia molecular desses parasitos são encorajadas. Uma possível estratégia para isso, é o estudo dos telômeros, estrutura fundamental para a homeostase do genoma. Os telômeros são estruturalmente diferentes do resto do cromossomo, e contam com proteínas específicas que realizam sua manutenção. A Replication Protein A subunit 1 (RPA-1) é uma proteína que interage de DNA de simples fita que tem diversas funções relacionadas com o metabolismo do DNA eucarioto, incluindo os telômeros. A RPA-1 é parte de um complexo heterotrimérico conservado nos eucariotos, incluindo Leishmania spp.. Recentemente nós mostramos por modelagem molecular que a estrutura terciária da LaRPA-1 difere dos seus ortólogos em humanos e leveduras, além de mostrar interações específicas nos telômeros dos parasitos, que na ausência de homólogos canônicos para telomere-end binding protein (TEP) elegem a LaRPA-1 como um potencial candidato para essa função. Neste trabalho, avaliamos a capacidade da LaRPA-1 como uma TEP, cujo papel principal é proteger a extremidade 3' dos telômeros de ataques por exonucleases. Uma busca estrutural por proteínas que compartilham com as TEP domínios de interação proteína-DNA, mostrou que no genoma de Leishmania spp. não existem homólogos estruturais para as mesmas. Aqui mostramos por diferentes abordagens que a LaRPA-1 tem a capacidade de interagir com no mínimo uma repetição telomérica e também é capaz de proteger in vitro a simples fita telomérica rica em G (5’ TTAGGG 3’) da digestão por Exonuclease I bacteriana cuja atividade é no sentido 3’-5’. Somando esses dados, com dados anteriores que mostram que a LaRPA-1 tem preferência pela fita telomérica rica em G e o fato dela ter sido co-purificada com a atividade de telomerase sugerem fortemente que ela está diretamente relacionada com a manutenção da maquinaria telomérica, podendo inclusive ser considerada a principal ligante de simples fita telomérica rica em G (3’ G-overhang) em Leishmania spp.
Among the protozoa parasites of the Leishmania genus are the causative agents of leishmaniasis, a neglected tropical disease endemic in many countries, including Brazil. Disease control and treatment are still inefficient and parasite drug resistance is a challenge. Therefore, efforts for the establishment of intensive research to better understand the molecular biology of these parasites are encouraged. One possible strategy is to study parasite telomeres, a vital chromosome structure important to maintain genome homeostasis. Telomeres are significantly different from the rest of the chromosome and are associated with proteins involved in their maintenance. Replication Protein A subunit 1 (RPA1), a single-stranded DNA-binding protein that plays multiple roles in eukaryotic DNA metabolism, including telomeres, is part of a conserved heterotrimeric complex which is present in most eukaryotes including Leishmania spp. Recently, using molecular dynamics simulations we have shown that the tertiary structure of LaRPA-1 differs from human and yeast RPA-1 and that it also shows parasitespecific interactions with telomeric DNA. In the absence of real homologues to telomere-end binding proteins, LaRPA-1 could be considered a potential candidate. If LaRPA-1 is a telomere-end binding protein, one of its main role would be to protect the telomeric 3`-end termini from nuclease attack. A structural search for proteins that share with the TEP domains of protein-DNA interaction, showed that in the genome of Leishmania spp. there are no structural homologues for them. In this work, we show by different methods, that in vitro LaRPA-1 can bind at least one telomeric repeat and it can also protect the telomeric G-rich sequence (5’ TTAGGG 3’) from the bacterial 3’-5’Exonuclease I digestion. These data compiled to previous data showing that LaRPA-1 preferentially binds the G-rich telomeric DNA and that it co-purifies with telomerase activity strongly suggest that LaRPA-1 is directly involved with parasite telomere maintenance and, possibly, is the main G-rich single-stranded (3’ G-overhang) telomere-binding protein in Leishmania spp.
AGUADO, PEREZ JULIO. "THE ROLE OF TELOMERIC RNA AT DYSFUNCTIONAL TELOMERES AND ITS IMPACT ON SENESCENCE AND AGING." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/556299.
Повний текст джерелаCESENA, DANIELE. "The RNA processing proteins Xrn1 and Rrp6 regulate DNA damage checkpoint activation and telomere metabolism." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/158272.
Повний текст джерелаGenome instability is one of the most pervasive characteristics of cancer cells. It can be due to DNA repair defects, failure to arrest the cell cycle and loss of telomere-end protection that lead to end-to-end fusion and degradation. Among the many types of DNA damage, the DNA Double Strand Break (DSB) is one of the most severe, because it can cause mutations and chromosomal rearrangements. Eukaryotic cells respond to DSBs by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR, in order to arrest the cell cycle until DSBs are repaired. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA) that arises upon nucleolytic degradation (resection) of the DSB. A similar checkpoint response is triggered when the natural ends of eukaryotic chromosomes lose their protection, resembling and being recognized as DSBs. This protection is provided by specialized nucleoprotein complexes called telomeres. Telomeric DNA consists of repetitive G-rich sequences that terminate with a 3’-ended single-stranded overhang (G-tail), which is important for telomere extension by telomerase. Several proteins, including the CST complex, are necessary to maintain telomere structure and length in both yeast and mammals. Emerging evidences indicate that RNA processing proteins play critical, yet poorly understood, roles in genomic stability and telomere metabolism. We provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 facilitate activation of Mec1/ATR by promoting the generation of RPA-coated ssDNA at intrachromosomal DSBs. Xrn1 and Rrp6 are also required to activate a Mec1/ATR-dependent checkpoint at uncapped telomeres due to loss of the CST component Cdc13. Xrn1 promotes checkpoint activation by facilitating the generation of ssDNA at both DSBs and uncapped telomeres. Xrn1 exerts this function at DSBs by promoting the loading of the MRX complex, whereas how it does at uncapped telomeres remains to be determined. By contrast, DSB resection is not affected by the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Finally, we demonstrate that Xrn1 maintains telomere length by promoting the association of Cdc13 to telomeres independently of ssDNA generation and exerts this function by downregulating the RIF1 transcript. Our results provide novel links between RNA processing and genome stability.
Gozaly, Chianea Yaghoub. "Investigation of telomere maintenance in BRCA2 defective mammalian cell lines." Thesis, Brunel University, 2014. http://bura.brunel.ac.uk/handle/2438/8724.
Повний текст джерелаWainwright, Linda Jane. "Studies of mean telomere length in human skin : changes with age and in malignancy." Thesis, University of Newcastle Upon Tyne, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260056.
Повний текст джерелаKhan, Sheik Jamaludin. "Functions of TRF2: From Telomere Protection to DNA Damage Signaling and Vascular Remodeling." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/123.
Повний текст джерелаHills, Mark. "The Xp/Yp telomere and its adjacent DNA : structure, sequence organisation and mutation." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/30355.
Повний текст джерелаJi, Yingjie, Xindi Dang, Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Jaun Zhao, Dechao Cao, Sushant Khanal, et al. "Topological DNA Damage, Telomere Attrition and T Cell Senescence During Chronic Viral Infections." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6522.
Повний текст джерелаBonnell, Erin. "The role of Tbf1 in telomere homeostasis in Saccharomyces cerevisiae." Mémoire, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/11077.
Повний текст джерелаEn différenciant les extrémités chromosomiques des cassures d’ADN internes, les télomères empêchent l'activation de la signalisation d’un dommage à l'ADN et fournissent une protection contre des activités inappropriées qui sont associées à une réparation de l'ADN. Une telle réparation pourrait en fait créer une instabilité génomique. Chez Saccharomyces cerevisiae, un nombre de protéines sont impliquées dans la structure du télomère et / ou la fonction de la élomérase. On pense que la protection des télomères est gérée par les répétitions télomériques et les protéines associées, mais il y a de plus en plus d’indices que la région sous-télomérique joue également un rôle. Cette région contient des sites de liaison pour plusieures protéines, notamment pour Tbf1. TBF1 est un gène essentiel et la protéine est impliquée dans l'homéostasie des télomères et dans la réponse aux dommages de l’ADN. Toutefois, les mécanismes moléculaires restent à être précisés. Mon projet de Maîtrise est basé sur l’observation que dans les cellules qui ont un allèle thermosensible (tbf1-ts), les télomères sont anormalement courts. Malheureusement, les 4 allèles mutants de tbf1 connus présentent tous des mutations ponctuelles multiples ce qui rend leur analyse difficile. Pour clarifier l'origine des variations phénotypiques de ces mutations, la mutagenèse dirigée a été utilisée pour créer des allèles tbf1 avec une seule mutation. Mes résultats montrent que deux mutations spécifiques, tbf1-82 et tbf1-453, causent des défauts de croissance cellulaires, ainsi qu'une sensibilité aux drogues qui endommageant l'ADN. Une analyse détaillée de ces nouveaux allèles de tbf1 a montré que la protéine pourrait avoir un rôle direct dans le maintien de la stabilité des télomères. Par exemple, en absence de la télomérase qui est responsable du maintien des télomères, les cellules entrent en sénescence réplicative après environ 60 générations et arrêtent de se diviser. Par contre, une petite fraction de la population est capable de contourner cet arrêt de croissance car ces cellules maintiennent les télomères par un processus dépendant de la recombinaison homologue. L'introduction de mutations tbf1 dans des souches sans télomérase provoque une accélération d’entrée en sénescence; donc Tbf1 est un régulateur précédemment inconnu de la sénescence. Divers tests génétiques avec des gènes de recombinaison homologue et des régulateurs de chromatine ont été effectués pour aider à caractériser TBF1 et ses interactions. La caractérisation de ces nouveaux allèles a permis de mieux comprendre les multiples rôles de Tbf1.
Zhou, Jia. "Dna Glycosylases Remove Oxidized Base Damages From G-Quadruplex Dna Structures." ScholarWorks @ UVM, 2015. http://scholarworks.uvm.edu/graddis/529.
Повний текст джерелаKargaran, Kobra. "The role of BRCA1 in telomere maintenance." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/13671.
Повний текст джерелаBourns, Brenda. "Development and characterization of a new assay to examine telomere-protein interactions in vivo /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/6336.
Повний текст джерелаLannan, Ford. "Folding of the human telomere sequence DNA in non-aqueous and otherwise viscous solvents." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/47598.
Повний текст джерелаLiew, Li Phing. "Characterization of the TLH1-4+ telomere-linked recq DNA helicase genes in schizosaccharomyces pombe." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510984.
Повний текст джерелаBeyer, Tracey Elaine, and Tracey Elaine Beyer. "Ontogeny of Unstable Chromosomes Formed by Telomere Replication Error." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/621103.
Повний текст джерелаBorssén, Magnus. "DNA methylation as a prognostic marker i acute lymphoblastic leukemia." Doctoral thesis, Umeå universitet, Patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127225.
Повний текст джерелаConway, Colin. "The role of Ku in antigenic variation, DNA repair and telomere maintenance in African trypanosomes." Thesis, University of Glasgow, 2002. http://theses.gla.ac.uk/30956/.
Повний текст джерелаBoerckel, Julie Ann Ahmed Shawn. "Isolation and characterization of genes involved in DNA damage response and telomere maintenance in Caenorhabditis elegans." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,843.
Повний текст джерелаTitle from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of PhD in the Department of Biology." Discipline: Biology; Department/School: Biology.
Eisenstatt, Jessica R. "Histone H4 Acetylation in the DNA Damage Response and Telomere Formation of Schizosaccharomyces pombe." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1440417554.
Повний текст джерелаLee-Bellantoni, Margaret S. "Antioxidant defense and redox responses to telomere homolog oligonucleotides in human dermal fibroblasts: a model for investigating redox signaling responses to DNA damage." Thesis, Boston University, 2005. https://hdl.handle.net/2144/37162.
Повний текст джерелаPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
It has been demonstrated that oligonucleotides homologous to the 3' telomere repeat sequence TTAGGG (T-oligos) stimulate DNA damage responses that are also induced by disruption of the telomere loop structure. Adaptive defense against oxidative stress and UV or ionizing radiation has been reported, but adaptive antioxidant defense as a response to mimicking telomere loop exposure has not been described. The T-oligos pTT and pGTTAGGGTTAG were added to human dermal fibroblast cultures to investigate whether mimicking telomere loop disruption stimulates antioxidant defense. pTT stimulated mitochondrial superoxide dismutase protein levels within 72 hours. Cell yields were higher after H202 exposure in fibroblasts pretreated with pTT for 72 hours compared to diluent pretreated cells. Intracellular reactive oxygen species (ROS) levels, measured by flow cytometry and the dichlorofluorescein diacetate probe, increased during T-oligo treatment as compared to diluent and oligonucleotide controls. The time course and degree of ROS stimulation corresponded to the time course for activation and/or induction of p53 and p21/Cip1/Waf1. The NADPH oxidase inhibitor diphenyliodonium chloride abrogated this increase and fibroblasts retrovirally transduced to produce dominant negative p53 failed to display increased ROS, implicating that the T-oligos induced ROS through p53-responsive NADPH oxidases. A horseradish peroxidase assay for extracellular H20 2 showed no H20 2 release with pTT treatment. To determine whether there was induction of senescence, an endpoint response to increased ROS and prolonged T-oligo treatment in fibroblasts, the senescence-associated β-galactosidase assay was conducted in parallel with the DCF assay. Only the 11mer T-oligo treatment modestly increased the number of β-galactosidase positive cells by 72 hours (<30% of cells). This is the first report suggesting that antioxidant defense and ROS signaling are part of the broad adaptive response in mammalian cells presumably initiated by telomere loop disruption and mimicked by T-oligos. T-oligo treatment thus offers a new model for studies of ROS signaling in human dermal fibroblasts, allowing exploration of the relationships between DNA damage, ROS, oxidative stress, and the evolution of cellular defense mechanisms.
2031-01-01
Jasti, Madhuri. "Identification and characterization of tac5, a telomerase activation mutant, characterization of DNA damage responses and assessment of interactions between telomere-related proteins in Arabidopsis thaliana." [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1238.
Повний текст джерелаDa, Silva Marcelo Santos 1982. "Estresse oxidativo em Leishmania amazonensis = do encurtamento dos telômeros ao deslocamento de LaRPA-1 do complexo telomérico = Oxidative stress in Leishmania amazonensis : from telomere shortening to displacement of LaRPA-1 from telomeric complex." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317093.
Повний текст джерелаTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A leishmaniose é um espectro de doenças causadas por parasitos do gênero Leishmania, que afeta milhões de pessoas em todo o mundo. Durante a infecção, os parasitos usam diferentes estratégias para sobreviver as defesas do hospedeiro, incluindo superar a exposição intensa a espécies reativas de oxigênio (ROS), principais responsáveis por causar danos no DNA, sobretudo nos telômeros, induzindo instabilidade genômica, senescência e morte celular. Telômeros são estruturas nos terminais dos cromossomos compostos por sequências de DNA repetitivas e proteínas, cuja função é proteger as extremidades dos cromossomos, evitando fusões terminais e degradação nucleolítica. Neste trabalho nós induzimos estresse oxidativo agudo em formas promastigotas de L. amazonensis através do tratamento com 2 mM de peróxido de hidrogênio (H2O2) por 1h, o qual foi capaz de aumentar os níveis de ROS intracelular, como demonstrado pela reação utilizando CM-H2DCFDA. Além disso, o estresse oxidativo induziu danos no DNA, como mostrado por análise quantitativa de 8-oxodG e núcleos positivos para o ensaio TUNEL. Observamos também, através de parâmetros qualitativos e quantitativos (Southern blot, telomere-PCR e flow-FISH), que o estresse oxidativo, assim como em mamíferos, induziu encurtamento dos telômeros. Analisando a co-localização e interação proteína:DNA por FISH-IIF e ensaios ChIP, foi possível demostrar que o estresse oxidativo causou erosão da extremidade 3¿G overhang, fazendo com que a proteína LaRPA-1 perdesse seu sítio de interação nos telômeros. Além disso, pudemos observar uma maior afinidade de LaRPA-1 para com a fita telomérica rica em C, nesse caso uma região de simples-fita gerada dentro da dupla fita telomérica, provavelmente como consequência do reparo de DNA, sugerindo a participação de LaRPA-1 na resposta a danos oxidativos. Por análise de curvas de crescimento e incorporação de EdU, foi possível observar que o estresse oxidativo induziu diminuição acentuada no número de parasitos em cultura, enquanto os sobreviventes continuaram proliferando e replicando DNA. Observamos também que o estresse oxidativo agudo provocou arrest de ciclo celular na fase G2/M em parte da população em crescimento exponencial. Em conjunto, esses resultados sugerem a presença de um sistema muito eficiente de resposta a danos oxidativos no DNA telomérico, que permite que os parasitos sobrevivam e repliquem DNA mesmo após um estresse agudo
Abstract: Leishmaniasis is a spectrum of diseases caused by parasites of the genus Leishmania that affects million people around the world. During infection, parasites use different strategies to survive host defenses including overcoming exposure to Reactive Oxygen Species (ROS), mainly responsible for causing DNA damage, especially at telomeres which frequently results in genome instability, senescence and cell death. Telomeres are chromosomes end termini structures composed by repetitive DNA coupled with proteins whose function is to protect chromosome ends and avoid end-fusion and nucleolytic degradation. In this work, we induced acute oxidative stress in promastigote forms of Leishmania amazonensis by treating parasites with 2mM hydrogen peroxide (H2O2) for 1 hour, which was able to increase intracellular ROS levels, as demonstrated by CM-H2DCFDA reaction. In addition, oxidative stress induced DNA damage, as confirmed by quantitative analysis of 8-oxodG and TUNEL-positive nuclei. We have also observed using qualitative and quantitative parameters (Southern blot, telomere-PCR and flow-FISH) that oxidative stress, as in mammals, induced telomere shortening. Analysing the protein:DNA co-localization and interaction by FISH-IIF and ChIP assays, it was possible to show that oxidative stress is able to induce erosion of the 3¿G overhang, inducing a displacement of LaRPA-1 from its telomeric interaction site. In addition, we observed an increase in the affinity between LaRPA-1 and the telomeric C-rich strand, in this case, a single-strand region inside the double-strand telomeric DNA generated probably as a consequence of DNA repair, suggesting the participation of LaRPA-1 in oxidative DNA damage response. Analysis of growth curves and EdU incorporation showed that oxidative stress induced a decrease in the number of parasites in culture, while the survivors continued proliferating and replicating DNA. Moreover, as result of acute oxidative stress, part of the parasites in exponential growth shows a G2/M cell cycle arrest. Taken together, these results suggest the presence of a very efficient oxidative damage response in the telomeres that allows parasites to survive and to replicate DNA even after acute stress
Doutorado
Genetica de Microorganismos
Doutor em Genetica e Biologia Molecular
Madalena, Christiane Rodriguez Gutierrez. "DNA repetitivo e seu papel na estrutura cromossômica terminal em Rhynchosciara americana (Diptera: Sciaridae)." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02102008-144225/.
Повний текст джерелаThe chromosomal localization of ribosomal DNA (rDNA) was studied in polytene and diploid tissues of four sciarid species, Trichosia pubescens, Rhynchosciara americana, R. milleri and Schwenkfeldina sp. While hybridization to mitotic chromosomes showed the existence of a single rDNA locus, ribosomal probes hybridized to more than one polytene chromosome region in all the species analyzed as a result of micronucleolar attachment to specific chromosome sites. Micronucleoli are small, round bodies containing transcriptionally active, probably extrachromosomal rDNA. In T. pubescens the rDNA is predominantly localized in chromosome sections X-10 and X-8. In R. americana the rDNA is frequently found associated with centromeric heterochromatin of the chromosomes X, C, B and A, and also with sections X-1 and B-13. Ribosomal probes in R. milleri hybridized with high frequency to pericentric and telomeric regions of its polytene complement. Schwfenkfeldina sp. displays a remarkably unusual distribution of rDNA in polytene nuclei, characterized by the attachment of micronucleoli to many chromosome regions. The results showed that micronucleoli preferentially associate with intercalary or terminal heterochromatin of all sciarid flies analyzed and, depending on the species, are attached to a few (Trichosia), moderate (Rhynchosciara) or a large (Schwenkfeldina sp.) number of polytene chromosome sites. This work also describes the characterization of chromosome end sequences of Rhynchosciara americana, initiated with the screening of a plasmid microlibrary made from a microdissected polytene chromosome end. We report the identification and sequencing of an R. americana satellite displaying base composition, genomic structure and chromosomal localization similar to the complex telomeric repeats of Nematocera that have previously been characterized. However, data obtained in other Rhynchosciara species, as well as distinct chromosomal localization of satellite and reverse transcriptase loci in R. americana, suggest that the repetitive element characterized does not reach the very end of the chromosome. The characterization of chromosome end sequences of Rhynchosciara americana continued with the screening of a phage library made with its genomic DNA. We choose pRaM47.33, a clone whose insert is a repetitive microsatellite characterized in the subtelomeric region of R. americana chromosomes, as a probe for the screening. We analyzed 12kb of a single phage insert, composed of M22 tandem arrays and a new microsatellite which was 16pb long, arranged in tandem (named M16). In situ hybridization showed the presence of M16 repeats in the five telomeric termini of R. americana chromosomes. The M16 repeat was used as a probe in another screen of the same phage library, which allowed us to analyze approximately 50kb of terminal DNA. We find that repetitive sequences, such as the 414pb repeat previously characterized in R. americana and stretches of Ramar1 and RaTART mobile elements, also characterized in R. americana, compose the subtelomeric region of R. americana chromosomes. Additionally, we find sequences that do not match sequences in the GenBank database and do not present repetitive motifs. Our results suggest that the telomeric regions of R. americana chromosomes are composed of more than one type of repetitive sequence.
dos, Santos Soares Martins de Castro Alicia Maria. "A mechanistic investigation into candidate markers of telomere-induced senescence in normal human epidermal keratinocytes." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8034.
Повний текст джерелаSmith, Zoe Elizabeth. "Analysis of the 16p telomere to examine the relationship between DNA replication, chromosome structure and gene expression." Thesis, University of Oxford, 1998. https://ora.ox.ac.uk/objects/uuid:fefcbb7b-9829-4a48-8edd-9608a613922d.
Повний текст джерелаNguyen, Lam Nhat, Juan Zhao, Dechao Cao, Xindi Dang, Ling Wang, Jianqi Lian, Ying Zhang, et al. "Inhibition of TRF2 Accelerates Telomere Attrition and DNA Damage in Naïve CD4 T Cells During HCV Infection." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6523.
Повний текст джерелаMusetti, Caterina Livia. "Heterocyclic Cations as Potential Anticancer Agents: An Approach that Targets G-quadruplex with Different Binding Modes." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/chemistry_theses/26.
Повний текст джерелаBUSNELLI, ANDREA. "MITOCHONDRIAL DNA COPY NUMBER, TELOMERE LENGTH AND DNA METHYLATION IN PERIPHERAL BLOOD OF WOMEN UNDERGOING IN VITRO FERTILIZATION CYCLES AS NEW PREDICTORS OF LIVE BIRTH." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/891706.
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