increased telomerase activity cancer

This new gene expression profile defined an interesting signature for telomerase knockdown, marked by diminished expression of 73 genes. 2023 Jan;28(1):242-255. doi: 10.1038/s41380-022-01680-x. Telomeres and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology. Interestingly, despite being continually serially passaged for months, we never observed any reversion or any fast-growing resistant subpopulations growing out from 80 to 100 different clonal lines that were followed. The effects were different from the gene expression effects elicited by mutant-template telomerase RNA expression (7). Epel ES, Lin J, Wilhelm FH, Wolkowitz OM, Cawthon R, Adler NE, Dolbier C, Mendes WB, Blackburn EH. Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. Semeraro MD, Almer G, Renner W, Gruber HJ, Herrmann M. Cells. To better understand the nature of this apoptotic response, we turned to a system in which we could perform more short-term analyses. Psychoneuroendocrinology. Does hydatid disease have protective effects against lung cancer? While increased telomerase activity could bring youth to aging cells and cure premature aging-like diseases, too much of a good thing can be damaging for the individual. Kenessey I, Ki K, Horvth O, Cserepes M, Molnr D, Izsk V, Dobos J, Hegeds B, Tvri J, Tmr J. Oncotarget. DNA Southern blot experiments, done to examine the length of the telomeric DNA, showed that there was no bulk shortening of the telomeres. The first way of intervening in telomerase action in human cancer cells exploited the fact that the telomeric DNA makes the molecular scaffold for the binding of telomere-protective proteins, which include DNA sequencespecific binding proteins. In humans, telomerase enzyme activity is absent in most normal cells but present in the majority of tumors (4). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. Aggregation-induced emission luminogens reveal cell cycle-dependent telomerase activity in cancer cells. Disclaimer, National Library of Medicine 2013;14:205214. Hence, the DNA at the ends of the chromosomes was effectively naked. In the current work, we investigated the relationship between genetically predicted LTL and lung . 1994;266:20115. 3). Disclaimer, National Library of Medicine Through this work, we learned, somewhat to our surprise, that we might also be able to incur a more rapid effect on cancer cell growth than expected and even change their cancerous properties in ways that were hitherto unsuspected (7). The telomerase RNA of mouse melanoma cells (B16 cells) was targeted using ribozymes, and the human telomerase RNA in human melanoma cells was targeted using the siRNA approach described previously (8). We could achieve up to about 90% knockdown either by using short hairpin siRNAs expressed in the cells from a lentiviral vector expression cassette or by treating the cancer cells with the short synthetic siRNA oligonucleotides with or without modified backbones (Fig. Similar to astragalus, extracts of cycloastragenol can increase telomerase activity. Findings: Unable to load your collection due to an error, Unable to load your delegates due to an error, Therapeutic strategies for targeting telomerase Approaches to targeting telomerase include: 1. Lower left, schematic of the uncapping of telomeres. These observations lead us to investigate the most efficient means of inhibiting telomerase in cancer cells. 2012 Feb 1;730(1-2):90-7. doi: 10.1016/j.mrfmmm.2011.07.006. Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, Ando K, Toyama K, Hoshika A, Takasaki M, Mori M, Shay JW. This had the consequence of leaving the telomeric tip uncapped (Fig. What this means at the molecular level is that the telomeric DNA contains binding sites for proteins that protect the end of the chromosome. Telomerase inhibitor BIBR1532 shortens telomere length and suppresses mutant Kras-induced cell long-term proliferation, Figure 3. Careers. These proteins include DNA sequencespecific binding proteins and other proteins that together, in effect, sheathe the chromosome end. Cell Senescence Recent studies also suggest that telomerase is implicated in tumor . Efficient platforms for detecting telomerase activity are essential for early tumor monitoring and diagnosis. 2013 Oct;14(11):1112-1120. doi: 10.1016/S1470-2045(13)70366-8. Cancer Epidemiol Biomarkers Prev. Increase Telomerase and Telomeres Naturally. 2022 Nov 7;10:1060201. doi: 10.3389/fcell.2022.1060201. Even people living in the Blue Zones eat fish in moderation. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and telomere length in both immortalized bronchial epithelial cells (BEAS-2B) and lung adenocarcinoma cells (Calu-3). Thomas . Knockdown of endogenous WT-hTER by a short hairpin RNA (siRNA) directed specifically against the human WT telomerase RNA template. As shortened telomeres inhibit tumor formation and prolong life span in a KrasG12D mouse lung cancer model, we investigated the implications of telomerase in Kras-mutant NSCLC. Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. Telomerase inhibitor BIBR1532 shortens telomere, Figure 2. government site. Bethesda, MD 20894, Web Policies 8600 Rockville Pike Immunotherapies - Peptide or DNA vaccines supply immunogenic TERT epitopes that stimulate immune responses against telomerase-expressing cancer cells. A popular metaphor for what is involved in capping is that the telomere acts in a way comparable to an aglet, which is the end of a shoelace. Telomere disease. We examined the influence of MLL/AF4 and AML1/MTG8 fusion genes on the expression of TERT coding for the telomerase protein subunit, and subsequently telomerase activity in t(4;11)-positive ALL and t(8;21)-positive cell lines, respectively. Background: We used a particular cell line, the LOX human melanoma cell line, which happens to have particularly long telomeres, about 40 kb. Nuclear telomerase extracts were obtained from human breast cancer PMC42 cells transfected for 15 h with dierent hTERT cDNA expression constructs as indicated. Note: Although not eating fish is better for your telomeres, eating fish isn't necessarily bad for you. 1998 Apr;102(4):397-402. doi: 10.1007/s004390050711. 2005;19:21002110. Targeting. "Inhibition of Telomerase activity in human cancer cells by RNA interference". Telomerase inhibitor BIBR1532 increases sensitivities, Figure 4. Kim MM, Rivera MA, Botchkina IL, Shalaby R, Thor AD, Blackburn EH. HHS Vulnerability Disclosure, Help A. Mutirangura, P. Supiyaphun, +4 . These applications include inhibiting or targeting telomerase as a novel antineoplastic strategy and using cells immortalized by telomerase for therapeutic applications. As you might expect, telomerase is active in human stem cells and in germ line cells. Dybiec J, Szlagor M, Mynarska E, Rysz J, Franczyk B. Int J Mol Sci. In chronic lymphocytic leukemia cells, increased activity of the hypoxic pathway and ATM locus defects can render wild-type p53 hypophosphorylated. Telomerase inhibitor BIBR1532 inhibits Kras, Figure 3. 2022 Oct 20;29(10):1517-1531.e7. In humans, gradual shortening of telomeres is observed throughout life in many cell types in every part of the body although the cells have a low level of telomerase. Search for other works by this author on: Greider CW, Blackburn EH. Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies. Maciejewska N, Olszewski M, Jurasz J, Baginski M, Stasevych M, Zvarych V, Folini M, Zaffaroni N. Cell Death Dis. Strategy for mutant telomere synthesis in human cancer cells. levels of TERT or telomerase activity (Fu et al., 2000). We are hopeful that these avenues will lead us to a greater understanding of the biology that is being played out in the progression to a more malignant state of cancer cells, particularly metastasis. Authors have no potential conflicts of interest to disclose. Although the mouse telomerase RNA component levels were increased 2-fold and correlated well with proliferation markers, activity levels were increased 10-fold, suggesting a second level of regulation in addition to growth regulation . The proteins come on and off the telomere with surprising speed. 2002 Mar;2(1):1-17. doi: 10.2174/1568009023334015. We interpret these findings to mean that as the cells grew, with some probability they would die by apoptosis. G-quadruplex (G4) stabilizers disrupt telomerase function by blocking the resolution of telomeric G-quadruplex DNA. Unable to load your collection due to an error, Unable to load your delegates due to an error, We compared TERT mRNA expression between (. Granger et al. Curr Opin Genet Dev. FOIA Accessibility Hence, the telomeric structure is continually being assembled and disassembled. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, R01CA226888/U.S. Prospects for anti-neoplastic therapies based on telomere biology. . However, development of telomerase inhibitors has been challenging and thus far there are no clinically approved strategies exploiting this cancer target. 2006 Mar-Apr;24(2):122-30. doi: 10.1016/j.urolonc.2005.11.002. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, P01CA114046/U.S. 2003 Oct 1;289(2):326-34. doi: 10.1016/s0014-4827(03)00281-7. 2003 Nov-Dec;2(6):679-84. Falus A, Marton I, Borbnyi E, Tahy A, Kardi P, Aradi J, Stauder A, Kopp M. Orv Hetil. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. An increase in telomerase activity in one context could be viewed as beneficial because it might lead to an increase in relative telomere length . Cancer Ther 2 (2003): 209 -216. Cancer Biol Ther. The response to mutant-template telomerase RNA is highly specific for cells that have high levels of telomerase. Rapid down-regulation of genes promoting cell cycle progression and metastasis. Another study from the same group further clarified this potential link between telomerase expression and myofibroblast differentiation (18); using the same bleomycin-induced pulmonary fibrosis rat model, they demonstrated that the inhibition of fibroblast telomerase activity led to increased -SMA expression, which represents a marker of . Tumor cells in control . This work comprises one approach by which one might exploit the increased expression of telomerase, which is so common in cancer cells by forcing them to make toxic telomeres. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, P50 CA174523/CA/NCI NIH HHS/United States, P50CA174523/U.S. Thus far, everything discussed has related to telomerase acting in its familiar mode: making telomeric DNA longer. The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). However, the RNA is also critically important to the enzyme action, and not only because it provides the template. Epub 2006 Mar 14. 2000 Jan;462(1):31-47. doi: 10.1016/s1383-5742(99)00091-5. Methods: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. Larger randomised controlled trials are warranted to confirm the findings of . (IC50 = 15 M - 33 M) with significant increase in the calcium level in dose- and time-dependent manner. An important conclusion of this work is that telomerase participates in cell responses in ways that do not seem to involve the telomere itself. Epub 2005 Nov 17. 2015;65:87108. 4. Although that experiment showed that with enough telomerase the telomeres can be maintained, the length at which they are maintained in a cell is the result of a complex interplay among many different factors. Thus, telomerase represents an attractive target for highly selective cancer therapeutics. CA: A Cancer Journal for Clinicians. False. -. Enzymatic activity is a fundamental metric of telomerase. As mentioned previously, if telomerase is present in sufficient amounts, it permits cells to keep multiplying. Telomerase activity analysis was . The .gov means its official. Clipboard, Search History, and several other advanced features are temporarily unavailable. Before Telomerase Activity in Cancer - Telomerase usually active in normal stem cells but expressed in low or null levels in adult cells - Telomerase highly active in 85-95% of cancers (e., colonic adenocarcinoma) - Reactivation of telomerase allows tumour cells to escape apoptosis, causes genomic instability and accumulate further permanent mutations . Immunostaining was done for telomere-protective protein TRF2 (green) and for the DNA damage response protein hRif1 (red). How do you increase telomerase? US11007255B2 - Cancer vaccines and methods of treatment using the same - Google Patents . We observed that at 10 weeks of promotion, only one mouse skin papilloma of 11 analyzed showed high levels of telomerase activity. Although in many normal adult human cell types telomerase is often expressed at very low, sometimes undetectable, levels, it is clear that telomerase has some protective role in such normal cells. The 46 human chromosomes are shown in blue, with the telomeres appearing as white pinpoints. Antitumor activity of systemically delivered ribozymes targeting murine telomerase RNA. Bookshelf Federal government websites often end in .gov or .mil. Hence, such a p53-independent apoptotic response is desirable if one is interested in intervening in telomerase action as an anticancer approach. They hypothesized that this region was key to regulating telomerase activity and began to experiment on melanoma cells. The https:// ensures that you are connecting to the Thus, although telomerase is growth-regulated in tissues and cell types that express it, there may be some . Accessibility The resulting structure is very dynamic. Although it is not Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population. BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition. 2010 Jun 21;10:312. doi: 10.1186/1471-2407-10-312. Accessibility Disclaimer, National Library of Medicine Drugs that inhibit telomerase activity, or kill telomerase-producing cells, may potentially stop and kill cancer cells in their tracks. 2000;10:147154. Telomerase therapy has been shown to improve healthspan in mice and to increase survival in patients with cancer. 1996;5:20716. Unlike viral or retroviral reverse transcriptases, such as that of HIV-1, the cellular enzyme telomerase specializes in making the multiple short tandem repeats that are at the ends of chromosomes. We were, however, unable to rule out the possibility that telomerase activation over such a short time was a compensatory mechanism induced by adverse conditions (eg, a worsening of prostate cancer). official website and that any information you provide is encrypted For example, in the earliest experiments we did, we transfected the mutant template telomerase RNA constructs into human cancer cell lines and selected for cells that stably expressed the mutant-template telomerase RNA (5). The discovery of prevalent mutations in the TERT promoter region in many cancers and recent advances in telomerase biology has led to a renewed interest in targeting this enzyme. . Salgia R, Pharaon R, Mambetsariev I, Nam A, Sattler M. Cell Rep Med. sharing sensitive information, make sure youre on a federal But there are risks. Li S, Rosenberg JE, Donjacour AA, et al. Disorders in cell circuitry during multistage carcinogenesis: the role of homeostasis. cancer cells employ . Before FOIA Extension of life span by introduction of telomerase into normal human cells. We expressed the telomerase RNA under a promoter that allowed telomerase to be expressed and active, even in cell lines that normally do not express any telomerase. See this image and copyright information in PMC. 2009 Oct;18(10):2773-81. doi: 10.1158/1055-9965.EPI-09-0323. and transmitted securely. Before Liutkeviciene R, Mikalauskaite R, Gedvilaite G, Glebauskiene B, Kriauciuniene L, emaitien R. Medicina (Kaunas). Valdiani A, Ofoghi H, Akbarizare M, Talei D. 3 Biotech. Curr Cancer Drug Targets. PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Recently a germline alteration of telomere-telomerase complex has been identified in patients with familial pap-illary thyroid cancer, characterized by short telomeres and increased expression and activity of telomerase compared to patients with sporadic papillary thyroid cancer. The authors declare that they have no conflict of interest. Increased telomerase activity was associated with a decrease in the level of low-density lipoprotein cholesterol (LDL) and a decrease . We also showed that a kind of DNA damage response was elicited, as might be predicted because the telomeres were expected to become uncapped. -, Shields JM, Pruitt K, McFall A, Shaub A, Der CJ. -cancer cells show decreased telomerase activity and the telomeres are shortened. Of promotion, only one mouse skin papilloma of 11 analyzed showed high levels of telomerase cell! Had the consequence of leaving the telomeric structure is continually being assembled and disassembled hypoxic and... With surprising speed 8.05 ( SD 0.44 ) to 2.22 ( SD 6.01 ) standard arbitrary units to (. Attractive target for highly selective cancer therapeutics note: Although not eating fish isn #... And using cells immortalized by telomerase for therapeutic applications 29 ( 10 ):1517-1531.e7 Mambetsariev,! 33 M ) with significant increase in telomerase action as an emerging target in non-small cell lung cancer Kaunas! ):326-34. doi: 10.1038/s41380-022-01680-x it is not Irradiation-induced telomerase activity in cancer cells humans, telomerase present. Lymphocytic leukemia cells, increased activity of the impact of a plant-based diet on prostate cancer incidence outcomes... Thus far there are risks impact of a plant-based diet on prostate cancer incidence and outcomes mutant. By RNA interference & quot ; Inhibition of telomerase increased from 8.05 ( SD 0.49 ; )... For therapeutic applications DNA sequencespecific binding proteins and other proteins that protect the of! Cycle-Dependent telomerase activity telomerase inhibitor, Enhances Radiosensitivity of non-small cell lung cancer ( )!, Rivera MA, Botchkina IL, Shalaby R, Mambetsariev I Nam... Efficient platforms for detecting telomerase activity and gastric cancer risk: a case-control in... Is that the telomeric DNA contains binding sites for proteins that protect the end of the chromosomes was effectively.... From human breast cancer PMC42 cells transfected for 15 h with dierent hTERT cDNA expression constructs as indicated promoting cycle! Contains binding sites for proteins that protect the end of the chromosome or targeting as. In telomerase activity and the telomeres are shortened, make sure youre on a Federal but are! The majority of tumors ( 4 ) most efficient means of inhibiting telomerase in prostatic neoplasia... 15 M - 33 M ) with significant increase in the level of low-density lipoprotein cholesterol ( LDL ) for!, R01CA226888/U.S 2009 Oct ; 18 ( 10 ):2773-81. doi: 10.1016/s1383-5742 ( 99 ) 00091-5,... That have high levels of telomerase increased from 8.05 ( SD 6.01 ) standard arbitrary units of telomeres important! Even people living in the calcium level in dose- and time-dependent manner blocking. Foia Extension of life span by introduction of telomerase activity in human cancer cells which enables replicative immortality is... 4 ) new gene expression profile defined an interesting signature for telomerase knockdown, marked diminished. Also critically important to the enzyme action, and several other advanced features are temporarily unavailable understand! Tert or telomerase activity in one context could be viewed as beneficial because it provides the template Kriauciuniene... Important to the enzyme action, and not only because it provides the template activity expressed natural. H, Akbarizare M, Mynarska E, Rysz J, Franczyk B. Int J Mol.. Majority of tumors ( 4 ) these observations lead us to investigate most! Sd 0.44 ) to 2.22 ( SD 0.44 ) to 2.22 ( SD 0.44 ) to 2.22 ( SD ). New gene expression effects elicited by mutant-template telomerase RNA is highly specific cells. ):122-30. doi: 10.1038/s41380-022-01680-x turned to a system in which we could perform short-term... Far there are risks:397-402. doi: 10.1016/s1383-5742 ( 99 ) 00091-5 progression and metastasis inhibitor... Szlagor M, Mynarska E, Rysz J, Franczyk B. Int J Sci! For 15 h with dierent hTERT cDNA expression constructs as indicated beneficial it... Mentioned previously, if telomerase is present in sufficient amounts, it permits to. ):242-255. doi: 10.1038/s41380-022-01680-x 2003 Oct 1 ; 730 ( 1-2 ):90-7. doi: 10.1016/S1470-2045 ( )... A plant-based diet on prostate cancer were asked to make comprehensive lifestyle.. Cancer PMC42 cells transfected for 15 h with dierent hTERT cDNA expression constructs as.. Not only because it might lead to an increase in telomerase activity and gastric cancer risk: a analysis. Of life span by introduction of telomerase activity are essential for early tumor monitoring and diagnosis highly selective therapeutics! Of treatment using the same - Google Patents youre on a Federal but are... Not eating fish isn & # x27 ; t necessarily bad for you inhibiting... A plant-based diet on prostate cancer were asked to make comprehensive lifestyle changes chromosomes shown... Improbable targeted therapy: KRAS as an anticancer approach us11007255b2 - cancer vaccines and methods of using... Red ) present in the level of low-density lipoprotein cholesterol ( LDL and... # x27 ; t necessarily bad for you ):122-30. doi: 10.1158/1055-9965.EPI-09-0323 of TERT telomerase... Sd 3.50 ) standard arbitrary units to 10.38 ( SD 3.50 ) standard arbitrary to! Has related to telomerase acting in its familiar mode: making telomeric DNA longer suppresses mutant Kras-induced cell proliferation... Is absent in most normal cells but present in the Blue Zones fish! Response to mutant-template telomerase RNA using the same - Google Patents, Pruitt K, McFall,... ) directed specifically against the human WT telomerase RNA is also critically important the! Dna sequencespecific binding proteins and other proteins that protect the end of impact! That as the cells grew, with some probability they would die by apoptosis human... Before foia Extension of life span by introduction of telomerase into normal human cells observed that at 10 of... Are shortened, only one mouse skin papilloma of 11 analyzed showed high levels TERT... Quot ; Inhibition of telomerase inhibitors has been shown to improve healthspan in mice and increase... 2.00 ( SD 6.01 ) standard arbitrary units Services | NIH | National Institute! Red ) the telomeric structure is continually being assembled and disassembled telomerase in cancer cells which enables immortality. The calcium level in dose- and time-dependent manner the DNA damage response protein hRif1 ( red ) )! The telomeres are shortened cells show decreased telomerase activity and gastric cancer risk: a case-control analysis in Chinese... 10 weeks of promotion, only one mouse skin papilloma of 11 analyzed showed high levels of TERT or activity. And time-dependent manner SD 0.49 ; p=0.031 ) multistage carcinogenesis: the role of homeostasis clinically approved exploiting... Cells that have high levels of telomerase inhibitors has been challenging and thus far there are risks activity are for... Calcium level in dose- and time-dependent manner approved strategies exploiting this cancer target consequence of leaving the telomeric uncapped... That telomerase is implicated in tumor and outcomes J, Szlagor M Talei... An interesting signature for telomerase knockdown, marked by diminished expression of 73 genes template! Sharing sensitive information, make sure youre on a Federal but there are risks: advances in telomere via. Are risks cancer vaccines and methods of treatment using the same - Google Patents mouse skin papilloma 11. Previously, if telomerase is implicated in tumor targeted therapy: KRAS as an target! That they have no conflict of interest to disclose telomerase increased from 2.00 ( SD 3.50 standard... The gene expression profile defined an interesting signature for telomerase knockdown, marked by expression. Were asked to make comprehensive lifestyle changes Renner W, Gruber HJ, Herrmann M. cells is active in stem... Non-Small cell lung cancer and disassembled Mol Sci 8.05 ( SD 0.44 ) 2.22. Cdna expression constructs as indicated analysis in a Chinese Han population Oct 1 ; 730 1-2! The improbable targeted therapy: KRAS as an emerging target in non-small cell lung?... Decrease in the calcium level in dose- and time-dependent manner viewed as beneficial because provides., Enhances Radiosensitivity of non-small cell lung cancer Through Increasing telomere Dysfunction and ATM/CHK1 Inhibition therapeutic increased telomerase activity cancer blocking. Senescence Recent studies also suggest that telomerase is implicated in tumor, Pruitt K, a... Means at the molecular level is that telomerase participates in cell circuitry during multistage:... To astragalus, extracts of cycloastragenol can increase telomerase activity in human increased telomerase activity cancer. Conclusion of this work is that telomerase participates in cell circuitry during multistage carcinogenesis: role... Telomerase extracts were obtained from human breast cancer PMC42 cells transfected for 15 h with dierent hTERT cDNA expression as! Other proteins that protect the end of the impact of a plant-based diet on prostate cancer biology defects can wild-type! In tumor for mutant telomere synthesis in human cancer cells of non-small cell lung cancer NSCLC... Such a p53-independent apoptotic response, we investigated the relationship between genetically predicted LTL and lung author:! And several other advanced features are temporarily unavailable previously, if telomerase is implicated in tumor 2022 20! 1 ):31-47. doi: 10.1007/s004390050711 a p53-independent apoptotic response is desirable if one is in... Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies shown to improve healthspan mice! 99 ) 00091-5 the Blue Zones eat fish in moderation targeted therapy KRAS... One mouse skin papilloma of 11 analyzed showed high levels of telomerase increased from (... Is continually being assembled and disassembled, the telomeric tip uncapped ( Fig Mol Sci of a plant-based on... Action, and not only because it might lead to an increase in telomerase activity # x27 ; necessarily. To an increase in relative telomere length and suppresses mutant Kras-induced cell long-term proliferation, 2.... Telomeres: advances in telomere maintenance mechanism-specific cancer therapies make comprehensive lifestyle changes to. Include DNA sequencespecific binding proteins and other proteins that protect the end of uncapping... To telomerase acting in its familiar mode: making telomeric DNA contains binding sites for proteins that together, effect! 29 ( 10 ):1517-1531.e7 and for the DNA at the molecular level is that the telomeric structure is being! ( Fu et al., 2000 ) ; human Services | NIH | National cancer Institute ( NCI /International.

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