ライフサイエンスコーパス: telomerase

1 er than 40 bp are inefficiently extended by telomerase.

2 tion of the G-rich strand of the telomere by telomerase.

3 o Pif1 action, thereby enabling extension by telomerase.

4 endent manner, in mouse cells overexpressing telomerase.

5 t synthesis by a reverse transcriptase named telomerase.

6 activities, including telomere elongation by telomerase.

7 er from epidermal growth factor receptor and telomerase.

8 and regulates Cajal body localization of the telomerase.

9 ten during replication and are lengthened by telomerase.

10 h (L)] patch, the surface of TPP1 that binds telomerase.

11 tracellular cues in a fashion independent of telomerase.

12 A, similar to that observed in cells lacking telomerase.

13 to investigate the function of telomeres and telomerase.

14 uman fibroblasts also showed upregulation of telomerase.

15 Tightly controlled recruitment of telomerase, a low-abundance enzyme, to telomeres is esse

16 t through promoting the binding of Ccq1 to a telomerase accessory protein Est1.

17 Telomerase action at telomeres is essential for the immo

18 Furthermore, we find that telomerase action at telomeres requires formation and re

19 lin knockout cells, with distinct changes in telomerase action.

20 re of telomeric C-strand synthesis following telomerase action.

21 Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (A

22 Presently, it is not known if telomerase activation is necessary for the proliferation

23 ction mutations in these cases suggests that telomerase activation is not only safely tolerated but a

24 In this study, we found that telomerase activation is not required for the short- ter

25 occurred by either telomere recombination or telomerase activation mechanisms.

26 t of microvessels from CAD patients with the telomerase activator AGS 499 converted the PEG-catalase-

27 Here, we delineate side chains in the telomerase active-site cavity important for repeat addit

28 RISPR-Cas9 or siRNA knockdown led to reduced telomerase activities and shortened telomere length, sug

29 ave found that CIRP is necessary to maintain telomerase activities at both 32 degrees C and 37 degree

30 P-dependent manner to compensate for reduced telomerase activities.

31 We show that telomerase activity and cardiomyocyte telomere length de

32 Our analysis integrates TERT abnormalities, telomerase activity and genomic alterations with telomer

33 Depleting TERRA increases telomerase activity and induces telomeric pathologies, i

34 We also used direct telomerase activity and nucleic acid binding assays to e

35 s nucleic acid substrates leading to loss of telomerase activity and processivity.

36 f ZNF148 results in reduced TERT expression, telomerase activity and telomere length.

37 Here we show that telomere length and telomerase activity are impaired in primary lymphocyte s

38 By measuring telomerase activity at the single-cell level using quant

39 Moreover, TSI requires telomerase activity but is independent of the functional

40 , this approach affords high sensitivity for telomerase activity detection and it can be regarded as

41 Using this strategy, the telomerase activity extracted from 10 cultured cancer ce

42 In the prolonged absence of telomerase activity in dividing cells, telomeres eventua

43 e reverse transcriptase (TERT) reconstitutes telomerase activity in the majority of human cancers.

44 tutions that disrupt the base triples reduce telomerase activity in vitro NMR studies also reveal tha

45 doknot (t/PK) and CR4/5 domains required for telomerase activity in vitro.

46 Notably, telomerase activity is affected in a gene dose-dependent

47 ation and experimental results indicate that telomerase activity is maximized on AuNP surface under g

48 Telomerase activity is not readily detected in resting h

49 in protein-protein interactions, regulating telomerase activity or DNA-binding.

50 Consistently, addition of Pop1 allows for telomerase activity reconstitution with wild-type telome

51 Minimally, telomerase activity requires a templating RNA and a cata

52 t only a subset of CD28+ T-cells have robust telomerase activity upon stimulation and are capable of

53 rget recognition, embodied by assay of human telomerase activity with DNA-conjugated gold nanoparticl

54 ric hybrid G-quadruplex and strongly inhibit telomerase activity with IC50 of 600 nM.

55 associated with increases in TERC stability, telomerase activity, and telomere elongation.

56 he structural basis of human and Tetrahymena telomerase activity, assembly, and interactions.

57 suppressing c-Myc expression, or inhibiting telomerase activity, caused telomere dysfunction and pro

58 ree, and highly sensitive detection of human telomerase activity, extracted from A549 cells.

59 e aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL.

60 ons and transcript fusions and predictive of telomerase activity.

61 ree specialized retroelements rather than by telomerase activity.

62 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition.

63 The reverse transcriptase telomerase adds telomeric repeats to chromosome ends.

64 regulating the recruitment and activation of telomerase, an enzyme that extends telomeric DNA.

65 Because ~90% of primary human tumors express telomerase and generally maintain very short telomeres,

66 protein subunit reverse transcriptase of the telomerase and its nucleic acid substrates leading to lo

67 short telomeres as a result of mutations in telomerase and other telomere components.

68 ls lacking any form of telomere maintenance (telomerase and telomere recombination).

69 c interactions between the rapidly diffusing telomerase and the chromosome end.

70 ation forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rte

71 volutionary predecessors of retrotransposon, telomerase, and retroviral RTs as well as the spliceosom

72 and, remarkably, structurally distinct RNPs, telomerase, and RNases P/MRP from unrelated progenitor R

73 However, only PrimPol, DNA polymerase alpha, telomerase, and the mitochondrial human DNA polymerase (

74 s of domains of TR and TERT as well as other telomerase- and telomere-interacting proteins have provi

75 The expression and activity of the telomerase are tightly regulated, and aberrant activatio

76 the ribonucleoprotein reverse transcriptase, telomerase, are associated with the bone marrow failure

77 o investigate additional rationale for human telomerase assembly as H/ACA RNP, we developed a minimiz

78 To analyze telomerase at its low endogenous expression level, we ge

79 ferent mechanisms, both 8oxoG and Tg enhance telomerase binding and extension activity to the same de

80 In this context, we establish that telomerase binding to reversed replication forks inhibit

81 l, we elucidate trafficking requirements for telomerase biogenesis and function and expand mechanisms

82 dow into the complex nature of telomeres and telomerase by permitting researchers to directly visuali

83 Here we present the structure of the human telomerase C-terminal extension (or thumb domain) determ

84 Telomerase can generate a novel telomere at DNA double-s

85 cers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length.

86 Purified human telomerase catalyzes processive repeat synthesis, which

87 by TPMs requires a gradual up-regulation of telomerase, coinciding with telomere fusions.

88 ce here that CIRP associates with the active telomerase complex through direct binding of TERC and re

89 nvolved in the formation of H/ACA snoRNP and telomerase complexes, both involved in essential cellula

90 ere than that of loss-of-function alleles in telomerase components, we hypothesized that PARN would a

91 g how individual components of telomeres and telomerase contribute to function.

92 y occurring mutations within this portion of telomerase contribute to human disease.

93 Telomerase counteracts the loss of terminal DNA sequence

94 features distinct from those associated with telomerase defects (e.g., dyskeratosis congenita).

95 f nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases.

96 Telomerase deficiency in patients with CHH is not mediat

97 hortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis c

98 In such mice, after several generations of telomerase deficiency telomeres shorten to the point of

99 Our studies provide mechanistic insight into telomerase-deficiency diseases and encourage the develop

100 Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (

101 g telomerase, whereas, in tissues expressing telomerase (e.g., bone marrow), the truncations are heal

102 interaction, to achieve temporally regulated telomerase elongation of telomeres.

103 Telomerase emerged during evolution as a prominent solut

104 Telomere elongation through telomerase enables chromosome survival during cellular p

105 Telomerase enzymatic activity was not directly affected

106 e in trans with TERT and reconstitute active telomerase enzyme in vitro The upstream essential domain

107 ith TERT promoter mutations showed increased telomerase expression and activity compared with cell li

108 Together, our data indicate that the lack of telomerase expression in most human somatic cells result

109 senescence, suggesting that reactivation of telomerase expression in senescent cells is an early eve

110 Our data confirm that telomerase expression protects against double-strand DNA

111 city, cytokine secretion, proliferation, and telomerase expression.

112 e structural properties of telomeric DNA and telomerase extension activity.

113 proteins from ciliate as well as vertebrate telomerase fit and function together as well as unexpect

114 Mice lacking telomerase (for example, mTR(-/-) telomerase RNA templat

115 ase RNA in nucleoli, a process that excludes telomerase from DNA repair sites.

116 dent sumoylation in the spatial exclusion of telomerase from sites of DNA repair.

117 e found that these modifications can perturb telomerase function in hPSCs and cancer cells, resulting

118 with TERT and species-specific proteins, and telomerase function in vivo requires interaction with te

119 he mechanism by which these mutations impact telomerase function remains unknown.

120 Mutations that compromise telomerase function result in stem cell failure diseases

121 es can arise from only small perturbation of telomerase function.

122 racting proteins have provided insights into telomerase function.

123 epeat addition processivity as essential for telomerase function.

124 ribonuclease (PARN), another gene linked to telomerase function.

125 Repression of telomerase gene promoter requires human-specific genomic

126 These findings indicate that telomerase gene therapy represents a novel therapeutic s

127 atients with CHH is not mediated by abnormal telomerase gene transcript levels relative to those of e

128 els, sex hormones regulate expression of the telomerase gene.

129 ly regulated, and aberrant activation of the telomerase has been observed in >85% of human cancers.

130 Then after telomerase has extended the G-rich strand, CST facilitat

131 These findings demonstrate that Tetrahymena telomerase holoenzyme and RPA complexes share subunits a

132 1 gene, functions as a core component of the telomerase holoenzyme as well as ribonuclear protein com

133 ase was unaffected by the elimination of the telomerase holoenzyme Cajal body chaperone TCAB1 or the

134 The Tetrahymena telomerase holoenzyme catalytic core (p65-TER-TERT) was

135 The role of telomerase holoenzyme components in gene expression and

136 In the ciliate Tetrahymena thermophila, the telomerase holoenzyme consists of TER, TERT, and eight a

137 o-electron microscopy map of the Tetrahymena telomerase holoenzyme has provided a framework for under

138 complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active

139 that revealed that, unlike other Tetrahymena telomerase holoenzyme subunits, Teb2 and Teb3 are not te

140 ic disorders are associated with an impaired telomerase holoenzyme that is unable to correctly assemb

141 We conclude that in the telomerase holoenzyme, instead of binding DNA, Teb2 and

142 se RNA and are essential constituents of the telomerase holoenzyme.

143 o share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins

144 rate limiting catalytic protein component of telomerase (hTERT) that is determined by the length of t

145 The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTER

146 A workflow was established using telomerase-immortalized human epithelial cells that reve

147 n the response of pocket epithelium-derived, telomerase-immortalized human gingival keratinocytes (TI

148 lucose and KSHV replication, we xeno-grafted telomerase-immortalized human umbilical vein endothelial

149 Telomerase-immortalized lines of control and R258C human

150 We recently showed that even early after telomerase inactivation (ETI), yeast cells have accelera

151 Our results lead us to propose that telomerase inappropriately binds to and inhibits restart

152 ernative lengthening of telomeres (ALT) is a telomerase independent telomere maintenance mechanism th

153 ration, including cells immortalized via the telomerase-independent ALT mechanism.

154 of stemness can be regarded as a conserved, telomerase-independent effect of dyskerin dysfunction.

155 ernative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism th

156 nds have also shown a potent nanomolar human telomerase inhibition activity and apoptosis induction.

157 was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle.

158 ccharomyces cerevisiae, the Pif1 helicase, a telomerase inhibitor, lies at the interface of these end

159 Notably, these cells were refractory to telomerase inhibitors, indicating recombination can prov

160 RNA-binding protein (CIRP or hnRNP A18) as a telomerase-interacting factor.

161 together as well as unexpected insight into telomerase interaction at telomeres.

162 However, how TEL-patch-telomerase interaction integrates into the overall orche

163 Telomerase is a nuclear regulator of telomere elongation

164 Telomerase is a ribonucleoprotein that maintains the end

165 Reactivating TERT and hence reconstituting telomerase is an important step in melanoma progression

166 Telomerase is an RNA-protein complex that extends the 3'

167 Telomerase is an RNA-protein complex that includes a uni

168 ing aging, while inappropriate activation of telomerase is associated with approximately 90% of cance

169 and generally maintain very short telomeres, telomerase is carefully regulated, particularly in large

170 heterogeneous population of T cells, even if telomerase is detected.

171 Telomerase is distinct among polymerases in its reiterat

172 Telomerase is expressed in early human development and t

173 ort telomeres lead to genome instability and telomerase is further up-regulated to sustain cell proli

174 et may lead to a better understanding on how telomerase is regulated and functions in immune cells.

175 Telomerase is the essential reverse transcriptase requir

176 Telomerase is the ribonucleoprotein enzyme that replenis

177 Although telomerase is thought to be involved in tumor angiogenes

178 phocytes, however upon antigen presentation, telomerase is transiently upregulated.

179 kerin and somatic stem cell maintenance in a telomerase-lacking organism, indicating that loss of ste

180 st identified in the Tetrahymena thermophila telomerase LARP7 protein p65.

181 POT1(CP)was defective in regulating telomerase, leading to telomere elongation rather than t

182 G2 silencing in normal human cells that lack telomerase led to increased recombination at telomeres,

183 nd tissue failure syndromes, while increased telomerase levels are associated with tumorigenesis.

184 Surprisingly, the Tg lesion stimulates telomerase loading and activity to a similar degree as a

185 Telomerase maintains chromosome ends from humans to yeas

186 Telomerase maintains genome integrity by adding repetiti

187 Telomerase maintains telomere length at the ends of line

188 Thus, telomerase-mediated G-strand extension and CST-mediated

189 net G-strand growth is apparent, indicating telomerase-mediated G-strand extension.

190 that protects chromosome ends and regulates telomerase-mediated telomere extension.

191 illicit DNA damage responses and to enhance telomerase-mediated telomere extension.

192 Tpz1, and Poz1 are important for regulating telomerase-mediated telomere synthesis and thus telomere

193 TAGGGT 3'-ending overhangs, indicating that telomerase-mediated telomere synthesis is important for

194 Telomerase minimally comprises the catalytic telomerase

195 tive (HeLa, MCF-7, HCT-116, and HEK293T) and telomerase-negative cell lines (U2OS and GM847).

196 In telomerase-negative cells, the loss of Rad51 or Brh2 cau

197 mTert, reporter was stringently repressed in telomerase-negative human cells in a histone deacetylase

198 erevisiae, 41 of which are only expressed in telomerase-negative yeast.

199 ust repair DSBs while blocking the action of telomerase on these ends.

200 T. brucei telomerase plays a key role in maintaining telomere leng

201 ated TERC (telomerase RNA) gene knockouts in telomerase positive cell lines that resulted in long-ter

202 way does not trigger ALT, as FANCD2 depleted telomerase positive cells do not acquire ALT-like phenot

203 on of the telomeric lagging strands, whereas telomerase positive cells exhibited similar elongation b

204 By comparing these ALT cells with parental telomerase positive cells, we observed that ALT cells po

205 d in most human cell lines tested, including telomerase-positive (HeLa, MCF-7, HCT-116, and HEK293T)

206 By analyzing telomerase-positive cells and their human TERC knockout-

207 We found telomerase-positive normal and CS-B cells had increased

208 In telomerase-positive U. maydis, deletion of rad51 and blm

209 or via POT1 gives equivalent enhancement of telomerase processivity.

210 Teb1 and TEB, but not RPA, increased telomerase processivity.

211 ents depend on the direct interaction of the telomerase protein TERT with the telomeric protein TPP1.

212 Studies of telomerase provide unique insights into cellular require

213 In this strategy, telomerase reaction products, which immobilized on strep

214 a functional link between BRAF signaling and telomerase reactivation in melanomas.

215 structures of the molecules comprising these telomerase-recruiting pathways remain unknown.

216 nent Ccq1 during late S phase is involved in telomerase recruitment through promoting the binding of

217 Our results reveal that telomerase recruitment to telomeres is driven by dynamic

218 Inhibiting telomerase recruitment to telomeres, but not its activit

219 cooperates with the TLC1-Ku-Sir4 pathway for telomerase recruitment, whereas the C-terminal interface

220 n by the DNA damage response while promoting telomerase recruitment.

221 e such mutation (K170Delta), residing in the telomerase-recruitment factor TPP1, provides an excellen

222 integrates into the overall orchestration of telomerase regulation at telomeres is unclear.

223 he mechanism of long-recognized differential telomerase regulation in mammalian species.

224 To better understand telomerase regulation, we performed immunoprecipitations

225 The dynamic properties of telomeres and telomerase render them difficult to study using ensemble

226 s reveal distinct consequences of changes in telomerase repeat addition processivity and expression l

227 OT1aOB1 abolished DNA binding and diminished telomerase repeat addition processivity.

228 acity to bind telomeric DNA and to stimulate telomerase repeat addition processivity.

229 ll-known "telomere disorder." RMRP binds the telomerase reverse transcriptase (catalytic subunit) in

230 Here, we demonstrate that human telomerase reverse transcriptase (hTERT) activates vascu

231 LA-DR-restricted peptides derived from human telomerase reverse transcriptase (hTERT) and referred as

232 The human telomerase reverse transcriptase (hTERT) gene is repress

233 Transcriptional activation of the human telomerase reverse transcriptase (hTERT) gene, which rem

234 G-quadruplexes in the promoter of the human telomerase reverse transcriptase (hTERT) gene.

235 Human telomerase reverse transcriptase (hTERT) plays a key rol

236 The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is overexpress

237 Telomerase minimally comprises the catalytic telomerase reverse transcriptase (TERT) and telomerase R

238 ' ends of linear chromosomes, using a unique telomerase reverse transcriptase (TERT) and template in

239 Reactivation of telomerase reverse transcriptase (TERT) expression is fo

240 is of B-cell lymphoma DNA confirmed that the telomerase reverse transcriptase (TERT) gene promoter is

241 find a germline deletion in intron 3 of the telomerase reverse transcriptase (TERT) gene that predis

242 Differential regulation of telomerase reverse transcriptase (TERT) genes contribute

243 somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocy

244 Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes te

245 ize telomeric repeats, the catalytic subunit telomerase reverse transcriptase (TERT) uses the RNA sub

246 ver, tumorigenesis-associated genes IGF2 and telomerase reverse transcriptase (TERT) were overexpress

247 -occurrence of mutations in the promoter for telomerase reverse transcriptase (TERT), along with BRAF

248 Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved

249 Remarkably, with only binding sites for telomerase reverse transcriptase (TERT), minimized hTR a

250 Among 6,835 cancers, 73% expressed telomerase reverse transcriptase (TERT), which was assoc

251 s using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT).

252 ss various N-terminal fusion proteins of the telomerase reverse transcriptase from its endogenous loc

253 oted c-Myc-dependent expression of the human telomerase reverse transcriptase gene (hTERT).

254 be mediated through POT1/TRF2 and via human telomerase reverse transcriptase inhibition through JNK

255 The template for telomerase reverse transcriptase is within the RNA subun

256 ligo also inhibited mRNA expression of human telomerase reverse transcriptase, a catalytic subunit of

257 alter the overall stability or expression of telomerase reverse transcriptase, these rare genetic dis

258 Furthermore, recombinant AREG induced telomerase reverse transcriptase, which appeared to be e

259 lmonary fibrosis by activation of fibroblast telomerase reverse transcriptase-dependent proliferation

260 nds to a peptide sequence derived from human telomerase reverse transcriptase.

261 tative polymerase chain reaction using human telomerase reverse transcriptase.

262 Biological stability of human telomerase RNA (hTR) relies on H/ACA proteins, but other

263 ends of linear chromosomes using an integral telomerase RNA (TER) and telomerase reverse transcriptas

264 p sequencing, we show that the budding yeast telomerase RNA (TLC1 RNA) is spatially segregated to the

265 1 subunits via independent interactions with telomerase RNA (TLC1) and telomeric proteins Sir4 and Cd

266 ends of linear chromosomes using an integral telomerase RNA (TR) template.

267 telomerase reverse transcriptase (TERT) and telomerase RNA (TR) that provides the template for telom

268 rse transcriptase (TERT) and template in the telomerase RNA (TR), thereby helping to maintain genome

269 ents of RNase P and RNase MRP, bind to yeast telomerase RNA and are essential constituents of the tel

270 The telomerase RNA component (TERC) is a critical determinan

271 Overexpression of the telomerase RNA component, hTR, demonstrated that this pr

272 are as follows: (1) Ku specifically binds to telomerase RNA in a distinct, yet related, manner to how

273 er cell cycle-dependent sequestration of the telomerase RNA in nucleoli, a process that excludes telo

274 erase activity reconstitution with wild-type telomerase RNA in vitro.

275 (DC), wherein PARN deficiency leads to human telomerase RNA instability.

276 ce lacking telomerase (for example, mTR(-/-) telomerase RNA template mutants) provide a model for inv

277 between BC200 and the quadruplex-containing telomerase RNA was confirmed by pull-down assays of the

278 Here, we generated TERC (telomerase RNA) gene knockouts in telomerase positive ce

279 e holoenzyme subunits, Teb2 and Teb3 are not telomerase-specific.

280 findings highlight the unknown complexity of telomerase structural requirements for expression and fu

281 Telomerase supplements the tandem array of simple-sequen

282 ferative impairment was not a consequence of telomerase suppression.

283 y, the protein and the RNA components of the telomerase (TbTERT and TbTR) and TbKu are required for t

284 r studies uncover a novel link between MLH1, telomerase, telomere and genome stability.

285 for further analyzing the interplays between telomerase, telomere replication, and telomere recombina

286 rus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of ap

287 Telomerase (TERT) is overexpressed in 80% to 90% of prim

288 everse transcriptase, a catalytic subunit of telomerase that was reversed by JNK inhibition.

289 Rarely, telomerase, the enzyme that maintains telomeres, acts up

290 within three highly conserved regions of the telomerase thumb domain referred to as motifs E-I (thumb

291 Recruitment of yeast telomerase to telomeres occurs through its Ku and Est1 s

292 editing and single-molecule imaging to track telomerase trafficking in nuclei of living human cells.

293 We demonstrate that telomerase uses three-dimensional diffusion to search fo

294 Telomere maintenance by minimized telomerase was unaffected by the elimination of the telo

295 res that halt proliferation in cells lacking telomerase, whereas, in tissues expressing telomerase (e

296 ically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the en

297 Telomerase, which has been detected in almost all kinds

298 core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances th

299 Furthermore, telomerases with low processivity dramatically elongate

300 However, telomeres can be maintained by telomerases with lower than wild-type processivity.