Dissertação (mestrado)—Universidade de Brasília, Faculdade em Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2017. / Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2017-05-11T18:07:41Z No. of bitstreams: 1 2017_KatherinedeSouzaRodrigues.pdf: 1435247 bytes, checksum: 20a2e26006858194d3ebf9aa5289e1d8 (MD5) / Approved for entry into archive by Raquel Viana (raquelviana@bce.unb.br) on 2017-05-16T18:10:59Z (GMT) No. of bitstreams: 1 2017_KatherinedeSouzaRodrigues.pdf: 1435247 bytes, checksum: 20a2e26006858194d3ebf9aa5289e1d8 (MD5) / Made available in DSpace on 2017-05-16T18:10:59Z (GMT). No. of bitstreams: 1 2017_KatherinedeSouzaRodrigues.pdf: 1435247 bytes, checksum: 20a2e26006858194d3ebf9aa5289e1d8 (MD5) Previous issue date: 2017-05-16 / O câncer de mama é o mais comum em mulheres e é responsável por 23% dos novos casos de câncer. O seu diagnóstico precoce assume papel decisivo para um melhor prognóstico devido à sua etiopatogenia complexa e multifatorial, já que não pode ser prevenido. Desta forma, os esforços para melhoria dos indicadores do câncer de mama são direcionados na busca por medidas que antecipem seu diagnóstico. A telomerase, uma enzima importante no processo de carcinogênese, está presente na maioria dos tumores e apresenta indícios de ser um bom marcador molecular, por isso deve ser estudada para avaliar sua relação com o câncer de mama. Este estudo analisou o polimorfismo rs2736100 da telomerase em pacientes com câncer de mama e testou a correlação de tais dados com o prognóstico e variáveis clínicas diversas. Para isso, o DNA de pacientes com câncer de mama foi extraído, submetido a PCR com os primers da região do polimorfismo e sequenciado. Ao todo, 119 pacientes com câncer de mama aceitaram participar do estudo. Foi encontrada associação em diversas características gerais do paciente (altura, idade e IMC) e características do tumor (RE, RP e Ki67), reafirmando a importância deles na clínica para a definição do melhor e mais fidedigno prognóstico. Através do sequenciamento foi identificada a região do polimorfismo rs2736100 da telomerase em 63 amostras, divididos entre aqueles com detecção do genótipo GG e AG. Foi encontrada uma deleção em 11,11% da população estudada que ainda não foi relatada na literatura. Nosso estudo demonstrou que este polimorfismo tem algumas associações com variáveis clínicas e de prognóstico do câncer de mama. Entretanto, para o polimorfismo rs2736100 da telomerase ser utilizado como marcador prognóstico no câncer de mama estudos mais detalhados devem ser realizados para confirmar seu valor clínico. / Breast cancer is the most common in women and accounts for 23% of new cases of cancer. Its early diagnosis plays a decisive role for a better prognosis because of its complex and multifactorial etiopathogenesis, which can not be prevented. Thus, efforts to improve indicators of breast cancer are targeted seeking measures that anticipate their diagnosis. Telomerase, an important enzyme in the carcinogenesis process, is present in most tumors and shows signs of being a good molecular marker, so it should be studied to evaluate its relationship with breast cancer. This study analyzed the rs2736100 polymorphism of telomerase in breast cancer patients and tested the correlation of such data with the prognosis and various clinical variables. For this, the DNA of patients with breast cancer was extracted, subjected to PCR with primers and sequenced region of the polymorphism. In all, 119 breast cancer patients agreed to participate in the study. An association was found in several general patient characteristics (height, age and BMI) and tumor characteristics (ER, PR and Ki67), reaffirming their importance in clinical settings for the definition of the best and most reliable prognosis. Through sequencing the telomerase rs2736100 polymorphism region was identified in 63 samples, divided among those with GG and AG genotype detection. A deletion was found in 11.11% of the studied population that has not yet been reported in the literature. Our study demonstrated that this polymorphism has some associations with clinical and prognostic variables of breast cancer. However, for the rs2736100 polymorphism of telomerase to be used as a prognostic marker in breast cancer more detailed studies should be performed to confirm its clinical value.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2016. / Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2016-12-02T17:21:35Z No. of bitstreams: 1 2016_KarollynedaSilvaMorais.pdf: 1281173 bytes, checksum: b0efd37124c639ccd7ed0e47dc36d9f9 (MD5) / Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2017-01-04T18:32:10Z (GMT) No. of bitstreams: 1 2016_KarollynedaSilvaMorais.pdf: 1281173 bytes, checksum: b0efd37124c639ccd7ed0e47dc36d9f9 (MD5) / Made available in DSpace on 2017-01-04T18:32:10Z (GMT). No. of bitstreams: 1 2016_KarollynedaSilvaMorais.pdf: 1281173 bytes, checksum: b0efd37124c639ccd7ed0e47dc36d9f9 (MD5) / As células normais tem potencial proliferativo regulado, e na maioria dos tipos celulares, obedecem a um número determinado de ciclos. Para que uma célula possa proliferar indefinidamente e de forma autônoma e ser considerada uma célula de câncer, ela deve passar pelo processo de imortalização. Os telômeros estão intimamente relacionados com o processo de imortalização, pois encurtam a cada ciclo celular, limitando a capacidade proliferativa. A telomerase é uma enzima que restaura a integridade dos telômeros, e está presente em 85% dos tipos de câncer, o que a torna um potencial alvo terapêutico. O câncer de mama é o segundo tipo de câncer mais incidente em todo o mundo, e entre as mulheres é o primeiro em mortalidade. Dada a sua importância epidemiológica, foram utilizadas neste estudo linhagens de câncer de mama que expressam telomerase, MCF-7 e MDA-MB-231, submetidas a tratamentos de curto e longo prazo com o inibidor de telomerase MST-312. Este foi citotóxico para ambas as linhagens em tratamentos de curto prazo, com morte celular acentuada nas doses de 5 μM em MCF-7 e 10 μM em MDA-MB-231, efeito este que independe da crise telomérica. Após 18 semanas de tratamento em dose subtóxica do MST-312, as linhagens foram novamente submetidas aos ensaios de citotoxicidade. A linhagem de MCF-7 apresentou maior sensibilidade ao MST-312 após o tratamento de longo prazo, com sinais de senescência celular acentuadas nos grupos tratados com o inibidor e cariótipos característicos de crise telomérica. Enquanto que a linhagem MDA-MB-231 demonstrou sinais de aquisição de resistência à droga, não demonstrando senescência celular, e maior viabilidade celular no grupo tratado com MST-312 por 18 semanas, quando comparado com o grupo controle. Demonstrando que células que expressam telomerase respondem de maneira diferente ao mesmo inibidor. _________________________________________________________________________________________________ ABSTRACT / Normal cells show a limited potential proliferative, presenting a reduced number of cell cycles. For one cell to be able to proliferate indefinitely and it becomes a tumoral cell, it needs to suffer an immortalization process. The telomeres are closely relating to the immortalization cell process, once that to each cell cycle they are facing a shortening which limits the proliferative capacity of them. Additonally, the telomerase enzyme, the protein that plays an importante role in to restore the telomere integrity and is present in about 85% of câncer types, it became a potential therapeutic target. The breast câncer is the second câncer type with the major incidence in the world and the first cause of mortality by tumor among women. Due its epidemiologic importance, in this study were used two cell lineages of breast câncer which express the telomerase enzyme, MCF-7 and MDA-MB-231, which they were submitted to treatments of long and short duration with the telomerase inhibitor MST-312. Both cell lineages utilized in this work showed citotoxicity in the treatments of short duration, with accentuated death cell in response to 5 μM dose of MST-312 in MCF-7 and 10 μM dose in the MDA-MB-231, this effect probably is independent of telomeric shortening. After 18 weeks of treatment using sub-toxic doses of the MST-312 inhibitor, the cell lineages were submitted to citotoxicity essays. The MCF-7 lineage presented a sensibility more elevated during the treatment of long duration showing cell senescence signals more accentuated in the group treated with the inhibitor and with intrinsic karyotypes of telomeric crisis. As results, the cell lineage MDA-MB-231 demonstrated signals of resistence acquisition to drug employed in this work, without signals of cell senescece, and in the citotoxicity essay under 10 μM dose, it was showed a significative cell number of inviable cells in the control group in comparing to the group treated for 18 weeks with MST-312 inhibitor. These results demonstrate that cells which are able to express the telomerase enzyme can respond of different ways to the same inhibitor.

abstract: Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex. / Dissertation/Thesis / Ph.D. Biochemistry 2011

No description available.

by Chong Yin Yue. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 146-161). / Abstracts in English and Chinese. / Acknowledgments --- p.i / Abstract (English/Chinese) --- p.ii / Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.xi / Chapter I. --- INTRODUCTION --- p.1 / Chapter I.1. --- Central Nervous System Tumors --- p.1 / Chapter I.2. --- Histopathological Classification of Gliomas --- p.4 / Chapter I.2.1. --- Astrocytic Tumors --- p.4 / Chapter I.2.1.1. --- Diffuse Astrocytomas --- p.4 / Chapter I.2.1.1.1. --- Low Grade Diffuse Astrocytomas --- p.5 / Chapter I.2.1.1.2. --- Anaplastic Astrocytomas --- p.5 / Chapter I.2.1.1.3. --- Glioblastomas --- p.6 / Chapter I.2.1.2. --- Pilocytic Astrocytomas --- p.9 / Chapter I.2.1.3. --- Pleomorphic Xanthoastrocytomas --- p.10 / Chapter I.2.2. --- Non-Astrocytic Tumors --- p.10 / Chapter I.2.2.1. --- Oligodendroglial Tumors --- p.10 / Chapter I.2.2.2. --- Ependymal Tumors --- p.16 / Chapter I.2.2.3. --- Dysembryoplastic Neuroepithelial Tumors --- p.20 / Chapter I.3. --- Molecular Genetics in Gliomas --- p.21 / Chapter I.4. --- Telomeres and Telomerase --- p.29 / Chapter I.4.1. --- History --- p.29 / Chapter I.4.2. --- Telomeres --- p.30 / Chapter I.4.3. --- End Replication Problem --- p.32 / Chapter I.4.4. --- Telomerase --- p.34 / Chapter I.4.5. --- Telomerase Components --- p.36 / Chapter I.4.5.1. --- RNA Component --- p.36 / Chapter I.4.5.2. --- Protein Component --- p.39 / Chapter I.4.5.3. --- Catalytic Subunit --- p.40 / Chapter I.4.5.4. --- Telomeric Repeat Binding Factor 1 --- p.41 / Chapter I.4.6. --- Cellular Immortality and Aging --- p.42 / Chapter I.4.7. --- Detection of Telomerase Activity --- p.44 / Chapter I.4.7.1. --- Telomeric Repeat Amplification Protocol Assay --- p.44 / Chapter I.4.7.2. --- Other Detection Methods --- p.45 / Chapter I.4.8. --- An Overview of Telomerase Activity --- p.48 / Chapter I.4.9. --- Alternative Lengthening of Telomeres --- p.50 / Chapter I.4.10. --- Telomeres Suppressor Genes --- p.51 / Chapter I.4.11. --- Telomerase and pl6/pRb Pathway --- p.52 / Chapter I.5. --- Telomeres and Telomerase Studies in Brain Tumors --- p.54 / Chapter I.5.1. --- Telomerase Activity in Brain Tumors --- p.54 / Chapter I.5.2. --- Telomere Length in Brain Tumors --- p.57 / Chapter I.5.3. --- Telomerase RNA Component Expression in Brain Tumors --- p.57 / Chapter II. --- OBJECTIVES of STUDY --- p.59 / Chapter III. --- MATERIALS AND METHODS --- p.61 / Chapter III.l. --- Telomerase Activity Study --- p.61 / Chapter III.1.1. --- Specimens --- p.61 / Chapter III.l.2. --- Telomerase Extraction --- p.63 / Chapter III.1.3. --- Protein Concentration Measurement --- p.63 / Chapter III.1.4. --- RNase-treated Samples --- p.64 / Chapter III.l.5. --- TRAP Assay --- p.64 / Chapter III.1.5.1. --- TS Primer Labelling --- p.65 / Chapter III.1.5.2. --- TS Primer Extension And PCR Amplification --- p.65 / Chapter III. 1.6. --- Non-Denaturing Polyacrylamide Gel Electrophoresis --- p.66 / Chapter III.1.7. --- Data Analysis --- p.67 / Chapter III.1.8. --- Statistical Analysis --- p.67 / Chapter III.2. --- Telomere Length Study --- p.68 / Chapter III.2.1. --- Specimens --- p.68 / Chapter III.2.2. --- DNA Extraction --- p.70 / Chapter III.2.3. --- DNA Concentration Measurement --- p.71 / Chapter III.2.4. --- Analysis of Telomere Length by Southern Hybridization --- p.71 / Chapter III.2.4.1. --- DNA Digestion --- p.73 / Chapter III.2.4.2. --- Southern Blotting --- p.73 / Chapter III.2.5. --- Data Analysis --- p.76 / Chapter III.2.6. --- Statistical Analysis --- p.77 / Chapter III.3. --- hTERT and hTEP1 mRNA Expression Study --- p.78 / Chapter III.3.1. --- Specimens --- p.78 / Chapter III.3.2. --- RNA Extraction and DNase Treatment --- p.78 / Chapter III.3.3. --- Reverse Transcription-Polymerase Chain Reaction --- p.80 / Chapter III.3.3.1. --- Primer Design --- p.81 / Chapter III.3.3.2. --- Standard Protocol --- p.81 / Chapter III.3.4. --- Statistical Analysis --- p.84 / Chapter III.4. --- p16 and pRb Immunostaining --- p.85 / Chapter III.4.1. --- Specimens --- p.85 / Chapter III.4.2. --- Slide Preparation --- p.85 / Chapter III.4.3. --- Immunohistochemistry --- p.87 / Chapter III.4.4. --- Data Analysis --- p.88 / Chapter III.4.5. --- Statistical Analysis --- p.89 / Chapter IV. --- RESULTS --- p.90 / Chapter IV.1. --- Telomerase Activity Study --- p.90 / Chapter IV.2. --- Telomere Length Study --- p.96 / Chapter IV.3. --- hTERT and hTEPl mRNA Expression Study --- p.104 / Chapter IV.4. --- p16 and pRb Protein Expression --- p.109 / Chapter V. --- DISCUSSION --- p.115 / Chapter V. 1. --- Telomerase Activity in Gliomas --- p.115 / Chapter V.2. --- Telomere Length in Oligodendroglial and Ependymal Tumors --- p.122 / Chapter V.3. --- hTERT and hTEPl mRNA Expression in Oligodendroglial and Ependymal Tumors --- p.128 / Chapter V.4. --- Protein Expression ofpl6 and pRb in Oligodendroglial and Ependymal Tumors --- p.132 / Chapter V.5. --- Discussion on Telomerase Activity-Related Factors --- p.135 / Chapter V.6. --- Significance of Study and Clinical Application --- p.137 / Chapter V.7. --- Future Direction --- p.141 / Chapter VI. --- CONCLUSION --- p.143 / Chapter VII. --- REFERENCES --- p.146

Polychlorniated Biphenyls (PCBs), a group of 209 individual congeners, are ubiquitous environmental pollutants and classified as probable human carcinogens. Hallmarks of aging and carcinogenesis are changes in telomerase activity and telomere length. I hypothesize that PCBs modulate telomerase activity and telomeres via interference in gene regulation and generation of reactive oxygen species (ROS) resulting in the dysregulation of cell growth. To explore this possibility, I exposed human skin keratinocytes (HaCaT) to a synthetic airborne PCB mixture (CAM) and individual congeners, i.e. PCB28, PCB52, PCB126 and PCB153. To mimic the chronic human exposure to PCBs and the slow process of carcinogenesis, a long term exposure period of 48 days and beyond was employed. All PCB congeners and CAM reduced telomerase activity, telomere length and cell growth. Among all PCBs, PCB126 had the most pronounced effect with reduction in telomerase activity, telomere length, hTERT and hTR gene expression and cell growth, while increasing TRF1 & TRF2 gene expression. PCB126 elicited an increase in CYP1A1 mRNA, CYP1A1 activity, DHE and DCFH oxidation levels from days 6 to 48, suggesting that increased ROS might be a causative factor for the reduction in telomerase activity and telomere length. However, transduction with hTERT and hTR subunits partly rescued telomerase activity, while treatment with PEG-catalase did not rescue telomerase activity suggesting that telomerase subunits play an important role on PCB126 induced effects on telomerase activity and telomere length. Since cells with shortened telomeres may escape crisis through telomerase reactivation, PCB126 treatment was continued until day 90. A change in growth behavior was observed from day 54 to 90, with cells recovering the proliferation rate, and increasing c-Myc, hTERT, and hTR gene expression level, re-activating telomerase activity and re-elongating telomere length. TRF1 & 2 gene expression started to decrease after day 66. From day 78, no increase in CYP1A1mRNA and its activity as well as CYP1B1, ALDH3A1, UGT1A1 and AhRRmRNA was observed suggesting that the AhR response pathway may have been altered. This study shows for the first time that PCBs initially reduce telomerase activity, telomere length, and cell growth, and can later lead to telomerase re-activation, telomere lengthening and increased cell growth with modulation of the AhR receptor pathway. This observation has broad implications for chronic PCB exposure scenarios.

Telomere attrition is a natural process that occurs due to inadequate telomere maintenance. Once at a critically short threshold, telomeres signal the cell to cease division and enter a cell fate termed senescence. Telomeres can be elongated by the enzyme telomerase, which adds de novo telomere repeats to the ends of chromosomes. Mutations in the telomerase complex or telomere-related genes give rise to the premature aging disorder Dyskeratosis Congenita (DC). DC provides a unique model system to study human aging in relation to telomerase insufficiency and the subsequent accelerated telomere attrition. In this thesis, skin fibroblasts as well as keratinocytes and T-cells were analyzed from patients with Autosomal Dominant Dyskeratosis Congenita (AD DC) caused by a single allele mutation in the telomerase RNA component (TERC) that leads to telomerase haploinsufficiency. These cells were determined to have a severe proliferative defect and extremely short telomeres. It is demonstrated that the short telomeres in AD DC cells initiate a DNA damage response transduced by the p53/p21WAF/CIP pathway which mediate an elevation in steady-state levels of mitochondrially-derived superoxide and oxidative stress. Exogenous expression of the catalytic reverse transcriptase component of telomerase (TERT) activated telomerase in DC fibroblasts but resulted in reduced activity (~50% compared to control fibroblasts); however telomeres were successfully maintained, albeit at a short length. Simultaneous expression of both TERT and TERC led to robust telomerase activity and elongation of telomeres, indicating that TERC haploinsufficiency is a rate-limiting step in telomere maintenance in DC cells. Reconstitution of telomerase activity in AD DC cells ameliorated the proliferative defects, reduced the p53/p21WAF/CIP response and decreased oxidative stress. Increased superoxide and slow proliferation found in DC cells could also be mitigated by inhibiting p21WAF/CIP or by decreasing the oxygen tension to which the cells are exposed. Together, these results support the hypothesis that the insufficient telomerase leads to critically short telomeres which signal the activation of p21WAF/CIP, leading to increased steady-state levels of mitochondrial superoxide and metabolic oxidative stress as a means to engage senescence. These studies provide insight into mechanisms whereby shortened telomeres lead to premature aging in a humans and point to potential strategies to reduce the effects of tissue dysfunction in DC patients.

Due to the duration of human ageing, researchers must rely on models such as animals and cells. Replicative senescence and stress-induced premature senescence (SIPS) are two cellular models sharing many features. Although telomeres play a major role in replicative senescence, their involvement in SIPS is unclear. In this work, we first wanted to investigate how accurate models of ageing are. We published a new model of the evolution of human ageing, which offers a refined view of the evolution of ageing in humans and suggests that human models should be favoured. Though studying other mammals, reptiles, and birds may also be useful, we conclude that lower life forms such as yeast and invertebrates are not representative of the human ageing process. Secondly, we wanted to elucidate the importance of telomeres in SIPS and study gene expression and regulatory networks. Using a telomerase-immortalized cell line, we found no evidence that damage specific to the telomeres is at the origin of SIPS. In our published model, neither the TGF-â1 pathway nor telomeres appear to play a crucial role in SIPS. We suggest that widespread damage to the DNA causes SIPS and propose a rearrangement of gene expression networks as a result of stress. Moreover, we advise caution in using telomerase in anti-ageing therapies since telomerase expression may alter the normal cellular functions and promote tumorogenesis. Lastly, we published strategies to integrate the modern computational approaches to research ageing. Although we find it unlikely that a full understanding of ageing may be achieved within a near future, we argue that understanding the structure and finding key regulatory genes of the human ageing process is possible.

Tripterygium wilfordii (T. wilfordii , TW ), a wildly used herb medicine,was tested for anticancer effect on human myeloid leukemia cells, HL60 in this study. The extract powder of T. wilfordii induced the apoptosis of HL60 cells was demonstrated by morphological change, cell viability, DNA fragmentation and caspase-3 activity. However, normal human peripheral mononuclear cells remained viable under the same treatment. The T. wilfordii induced apoptosis of HL60 cells was associated with the increased Bax gene expression and decreased Bcl-2 gene expression. In addition, the gene expression of c-Myc, and hTERT, TP1, but not TR was downregulated in TW treatedHL60 cells in dose-dependent manner. Telomerase activity in HL60 cell was inhibited by the T. wilfordii . C-Myc protein is reported as a positive regulator of hTERT gene in HL60 cells. Therefore, proto-oncogene c-myc might play an essential role in the regulation of telomerase activity in HL60cells exposed to theT. wilfordii . All the treated cells showed a decrease in telomerase activity after T. wilfordii treatment. Taken togather, these results indicate that theT. Wilfordii-induced apoptosis in HL60 is mediated through mitochondrial pathway in parallel with the decrease expression of hTERT gene.

Telomerase is the key enzyme synthesizing telomeric DNA in most eukaryotic organisms. In mammals, telomerase expression is abundant in the germline cells but is undetectable in most other differentiated organs. Intensive studies of telomerase have focused on human cancerous cells, where over 90% of all cancerous tissues examined have telomerase activity. In wild-type Arabidopsis, telomerase expression is abundant in reproductive organs and dedifferentiated tissues such as flowers, siliques and calli but barely detectable in vegetative tissues (both rosette and cauline leaves). In this study, a biochemical screen strategy was developed for isolation of telomerase activating mutants in Arabidopsis thaliana. Through screening of Arabidopsis activation-tagged lines by a PCR-based TRAP assay, two tac (for telomerase activator) mutants were isolated. RT-PCR analysis of AtTERT expression revealed that different mechanisms are involved in alternating telomerase activity in tac1 and tac2. We cloned and characterized the TAC1 gene. TAC1 encodes a single zinc finger protein and acts synergistically with auxin to induce telomerase expression without altering cell cycles. Telomere length was unperturbed in the mutant, but other phenotypes, such as altered root development and the ability of cells to grow in culture without exogenous auxin, indicated that TAC1 not only is part of the previously reported link between auxin and telomerase expression, but also potentiates other classic responses to this phytohormone. DNA microarrays were used to analyze the expression profile of the tac1 mutant and revealed that several drought-induced genes were up-regulated 3 to 10 fold in the tac1-1D mutant. RT-PCR analysis further confirmed this up-regulation for five of these genes. Investigation of root growth also indicated that tac1-1D roots were ~20% longer relative to wild-type. Further experiments demonstrated that over-expression of TAC1 does confer drought tolerance, but not salt tolerance. In addition, our preliminary result showed that treatment with a low concentration of IAA could induce drought tolerance in wild-type Arabidopsis. Although plants with constitutive expression of telomerase have no practical utility, the ability of TAC1 to confer drought tolerance could have significant agricultural applications.