ライフサイエンスコーパス: shelterin

1 sequences bound by a unique set of proteins (shelterin).

2 g additional protection against resection by shelterin.

3 ificantly to the end protection functions of shelterin.

4 hinery that form a protective complex termed shelterin.

5 th DNA replication and telomere 'capping' by shelterin.

6 e the functional compartmentalization within shelterin.

7 ish whether TPP1 has additional functions in shelterin.

8 heterodimers that bind to other proteins in shelterin.

9 eres are protected by a six-protein complex: shelterin.

10 nt of a telomeric DNA/protein complex called shelterin.

11 tectable effect on other components of mouse shelterin.

12 ter of which results in the complete loss of shelterin.

13 architecturally and functionally similar to shelterin.

14 at are bound by a six-subunit complex called shelterin.

15 the proper capping of telomeric sequences by shelterin.

16 ains elusive due to the diverse functions of shelterin.

17 ological tools to investigate the biology of shelterin.

18 otective protein factors collectively termed shelterins.

19 while vertebrate telomeres are protected by shelterin, a complex of six proteins that does not inclu

20 Human telomeres are protected by shelterin, a complex that includes the POT1 single-stran

21 Human chromosome ends are capped by shelterin, a protein complex that protects the natural e

22 gh the interaction of telomeric repeats with shelterin, a protein complex that represses DNA damage s

23 The telosome/shelterin, a six-protein complex formed by TRF1, TRF2, R

24 Shelterin, a six-protein complex, plays a fundamental ro

25 Telomeres are coated by shelterin, a six-subunit complex that is required for pr

26 Human telomere function is mediated by shelterin, a six-subunit complex that is required for te

27 Telomeres are protected by shelterin, a six-subunit protein complex that represses

28 stead, the TRFH docking site of TRF2 binds a shelterin accessory factor (Apollo), which does not inte

29 e that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection o

30 heir shared binding partner (TIN2) and other shelterin accessory factors.

31 s recombination, and resection] and show how shelterin acts with general DNA damage response factors

32 insight into the functional consequences of shelterin alterations in ALT cells.

33 Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that

34 reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin-mediated compac

35 nism by which TPP1/POT1 heterodimers bind to shelterin and function in telomere protection.

36 information about the architecture of human shelterin and how it performs its functions at telomeres

37 ein interaction can disrupt the structure of shelterin and may be employed as pharmacological tools t

38 2 and RAP1) to form the six-protein telosome/shelterin and other subcomplexes.

39 In this perspective, we introduce shelterin and the mechanisms of ATM activation and NHEJ

40 cates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senesc

41 Our data reveal a remarkable plasticity in shelterin architecture and separate functions in length

42 Mutations that abrogate shelterin assembly or removal of individual subunits fro

43 operativity as a conserved driving force for shelterin assembly.

44 RF1, but not of TRF2, interacts with another shelterin-associated factor: PinX1.

45 SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PS

46 tures at lagging-strand telomeres to promote shelterin association and facilitate telomerase action a

47 ated telomeric repeats, thereby compromising shelterin binding to telomeric termini.

48 Here we show that TPP1 and POT1a/b in shelterin block a resection pathway distinct from that r

49 Biochemical analyses reveal that shelterin bridge assembly is a hierarchical process in w

50 mplex that provides the structural basis for shelterin bridge assembly.

51 pathway revealed here does not depend on the shelterins but rather on the unique character of telomer

52 We therefore conclude that shelterin can protect chromosome ends as a TRF2-tethered

53 ion of the telomeric DNA or by inhibition of shelterin, cells show the hallmarks of ataxia telangiect

54 The shelterin complex (POT1, TRF1, TRF2, Tin2, Rap1, and POT

55 l new information about the dysregulation of shelterin complex after silica inhalation in rats, and h

56 POT1 and TPP1 are part of the shelterin complex and are essential for telomere length

57 re 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome s

58 of TIN2 may allow dynamic remodeling of the shelterin complex and its associated factors during the

59 r genes and genes encoding components of the shelterin complex and related proteins.

60 The Shelterin complex associates with telomeres and plays an

61 The conserved multifunctional shelterin complex associates with telomeres to coordinat

62 lian cells: The reduced concentration of the shelterin complex at long telomeres results in TZAP bind

63 been proposed to form part of a six-protein shelterin complex at telomeres.

64 related to the abundance of TRF1 protein, a shelterin complex component in the telomere.

65 The TRF1 subunit of the shelterin complex controls telomere length by regulating

66 re attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a res

67 ssive telomere attrition or uncapping of the shelterin complex elicits a DNA damage response as a res

68 end-protection problem, we removed the whole shelterin complex from mouse telomeres through condition

69 Expression of shelterin complex genes was assessed in the lungs at 16

70 of silica exposure on the regulation of the shelterin complex in an animal model.

71 nd review emerging knowledge implicating the shelterin complex in hematological disorders.

72 ime the essential role of a component of the shelterin complex in the maintenance of HSC and progenit

73 tional interaction between MLL, p53, and the shelterin complex in the regulation of telomeric transcr

74 The shelterin complex is a macromolecular assembly of protei

75 The conserved shelterin complex is critical for chromosome capping and

76 Evolutionarily conserved shelterin complex is essential for telomere maintenance

77 This represents the first shelterin complex mutation linked to human disease and c

78 The shelterin complex plays dual functions in telomere homeo

79 The protection of telomere ends by the shelterin complex prevents DNA damage signalling and pro

80 The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a

81 Furthermore, two shelterin complex proteins TRF2/POT1 were found to be up

82 In fission yeast, the conserved telomeric shelterin complex recruits the histone H3K9 methyltransf

83 d how they find protein partners to form the shelterin complex remains uncertain.

84 d ATR and address the mechanism by which the shelterin complex represses these two important DNA dama

85 find that depletion of two components of the shelterin complex that is found at telomeres--TPP1 and t

86 Acd encodes Tpp1, a component of the shelterin complex that maintains telomere integrity, and

87 ation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the

88 of telomeres 1A (Pot1a), a component of the Shelterin complex that protects telomeres, improves haem

89 nally inactivating Pot1a, a component of the shelterin complex that stabilizes telomeres, within endo

90 NHP2), and recently in one component of the shelterin complex TIN2 (gene TINF2).

91 oes not depend on POT1 or interaction of the shelterin complex with the single-stranded region of the

92 ue to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeri

93 n TPP1)-mediated complete linkage within the shelterin complex, bridging telomeric dsDNA to ssDNA, co

94 g telomeres that have a low concentration of shelterin complex, competing with the telomeric-repeat b

95 encoding TPP1), a component of the telomeric shelterin complex, in one family affected by HH.

96 Binding Factor 1 (TRF1), a component of the shelterin complex, regulates the genome-wide binding of

97 Within the shelterin complex, TRF2 uniquely serves to protect telom

98 TRF1 is part of the shelterin complex, which binds telomeres and it is essen

99 Schmutz and de Lange discuss the shelterin complex, which binds to mammalian telomeres an

100 Mammalian telomeres are protected by the shelterin complex, which contains single-stranded telome

101 ng to find protein partners and assemble the shelterin complex, which in turn stabilizes the interact

102 investigating the molecular evolution of the shelterin complex, which protects telomeres, across 16 v

103 against the DNA damage response (DDR) by the shelterin complex.

104 hich in turn promotes proper assembly of the shelterin complex.

105 meres, repetitive DNA sequences bound by the shelterin complex.

106 omeric DNA repeats bound by the multiprotein shelterin complex.

107 able association of TRF1 with Tin2 to form a shelterin complex.

108 f TRF1, a primary component of the telomeric shelterin complex.

109 cal link between telomerase and the telosome/shelterin complex.

110 urs only following the removal of the entire shelterin complex.

111 CD), which is a part of the telomere-capping shelterin complex.

112 NA along with other components of the known "shelterin" complex.

113 ssays to measure the DNA binding activity of Shelterin complexes in human cell extracts.

114 mposition and DNA binding specificity of two Shelterin complexes: a 6-member complex that contains al

115 tion and demonstrate that TPP1 is the second shelterin component (in addition to TIN2) to be implicat

116 1(ATM)/Rad3(ATR)-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved

117 atin without affecting CLRC interaction with shelterin component Pot1, located at chromosome ends.

118 e have previously shown that deletion of the shelterin component Pot1b in the setting of telomerase h

119 lomere degradation due to the absence of the shelterin component POT1b.

120 spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuc

121 previously been found in telomerase and the shelterin component telomeric repeat binding factor 1 (T

122 n adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, c

123 ator in breast cancer cell expression of the shelterin component TERF1 (TRF1).

124 tween the SCF(FBX4) ubiquitin ligase and the shelterin component TIN2 controls TRF1 abundance and tel

125 of patients, however, show mutations in the shelterin component TIN2, a TRF1-interacting protein, pr

126 atients is heterozygous for mutations in the shelterin component TIN2.

127 The telomeric shelterin component TPP1 has critical functions in telom

128 the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomer

129 revealed that a patch of amino acids in the shelterin component TPP1, called the TEL-patch, is essen

130 cluster of amino acids on the surface of the shelterin component TPP1--is necessary for the recruitme

131 structurally similar to that adopted by the shelterin component TPP1.

132 The shelterin component TRF1 facilitates telomere replicatio

133 plication of telomeres is facilitated by the shelterin component TRF1.

134 icient duplication of telomeres requires the shelterin component TRF1.

135 re replication problem that is solved by the shelterin component TRF1.

136 o telomeres through its interaction with the shelterin component TRF1.

137 We used conditional deletion of the shelterin component TRF2 (also known as TERF2) from mous

138 Shelterin component TRF2 prevents ATM activation, while

139 telomere shortening or loss of the telomeric shelterin component TRF2.

140 es rendered dysfunctional by deletion of the shelterin component TRF2.

141 to telomeres through an interaction with the shelterin component TRF2.

142 monstrate that deletion of Ccq1, a telomeric shelterin component, rescued cell death after Aurora inh

143 ed mutations in ACD (c.752-2A>C) and another shelterin component, telomeric repeat binding factor 2,

144 plex interplay between the telomere-specific shelterin components and DNA repair proteins, (c) the no

145 Strikingly, we find that Shelterin components are required for interactions betwe

146 These analyses reveal an unexpected role for Shelterin components in genome reorganization in cells e

147 ta cells, suggesting that the missplicing of shelterin components is the cause of such defects, and t

148 elomere elongation while still retaining the shelterin components on telomeres.

149 terin components, rather than the individual shelterin components per se, defines the telomerase-none

150 ected in tls1Delta cells, including mRNAs of shelterin components rap1+ and poz1+.

151 Here we show that deletion of telomere shelterin components restores pericentric heterochromati

152 induced a significant downregulation of the shelterin components TRF1, TRF2, and POT1 at the transcr

153 n progressive HIV-1 infection, the two major shelterin components TRF2 and TPP1 are selectively reduc

154 come deprotected through the deletion of the shelterin components TRF2 or POT1.

155 The abundance of shelterin components was similar in primary and transfor

156 grity in a complex that is distinct from the shelterin components, Pot1 and Tpp1.

157 Therefore, the linkage within the shelterin components, rather than the individual shelter

158 in telomere length maintenance genes and in shelterin components, the protein complex that protects

159 chromosome ends and the proper connection of shelterin components, which allows CLRC to skip telomeri

160 mposed of telomeric repeats is recognized by shelterin components.

161 TRF1 is one of the best studied shelterin components; however, the molecular architectur

162 spreading and that artificial restoration of shelterin connections or increased heterochromatin sprea

163 Shelterin contains two closely related proteins (TRF1 an

164 at, in addition to TIN2, other components of shelterin contribute to the recruitment of TPP1/POT1a,b

165 3' overhang formation is thus a multistep, shelterin-controlled process, ensuring functional telome

166 Furthermore, we find that the human shelterin counterparts TPP1-TIN2-TRF2 also assemble hier

167 Through affinity purification, we found that shelterin directly associates with CLRC through the Ccq1

168 omere stability and nuclear organization via shelterin downregulation, in particular TRF2, favors chr

169 These data suggest that shelterin dysfunction and ensuing upregulation of the tu

170 rescue TPP1-deficient HSCs, indicating that shelterin dysfunction has unique effects in different st

171 coli single-stranded DNA-binding protein or shelterin factor Pot1, stimulated FANCJ ejection of TRF1

172 Similar to the human shelterin, fission yeast shelterin is composed of telome

173 ate the mechanism of six-protein complex (or shelterin) formation and the function of this complex.

174 The shelterin-free telomeres are processed by microhomology-

175 Notably, defective shelterin function and upregulation of p16(INK4a) remain

176 rk argued that miRNA-dependent regulation of shelterin function has a clinically significant impact o

177 stasis, there is little understanding of how shelterin function is limited in cancer cells.

178 rogressive and unsynchronized, acute loss of shelterin function represents an attractive alternative

179 ts of individual shelterin proteins, discuss shelterin functions in hematopoiesis, and review emergin

180 lterin genes, although little is known about shelterin functions in somatic stem cells.

181 are acutely sensitive to inactivation of the shelterin gene Acd, encoding TPP1.

182 arose as a founder mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T; p.Ser

183 ta can also arise from mutations in specific shelterin genes, although little is known about shelteri

184 TIN2, the central component of shelterin, has binding sites to three subunits: TRF1, TR

185 ions, and tethers, we define key elements of shelterin important for telomere length regulation.

186 These analyses reveal the role of Shelterin in facultative heterochromatin assembly at lat

187 Shelterin includes the heterodimeric POT1-TPP1 protein,

188 1 is more extensive upon complete removal of shelterin, indicating additional protection against rese

189 Shelterin is an essential telomeric protein complex that

190 imilar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific dou

191 In fission yeast, shelterin is comprised of five proteins.

192 Instead, shelterin is emerging as a protein complex with DNA remo

193 The current data argue that shelterin is not a static structural component of the te

194 es, indicating that some of the TPP1.POT1 in shelterin is not associated with the single-stranded tel

195 component of the telomere protection complex Shelterin, is required to assemble heterochromatin islan

196 mentation of AR with telomeric proteins in a shelterin-like mega complex.

197 g activity of shelterin and demonstrate that shelterin-mediated compaction of telomeric chromatin pro

198 ther analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi muta

199 hromatin assembly, Tls1-mediated splicing of shelterin mRNAs also regulates telomere length.

200 is highlights TPP1(L104A/L104A) as the first shelterin mutant engineered at the endogenous locus of h

201 ing rescued heterochromatin defects in these shelterin mutants.

202 Although many shelterin mutations affect subtelomeric heterochromatin

203 The telomeric complex, shelterin, plays a critical role in protecting chromosom

204 ingle-stranded DNA binding proteins in mouse shelterin, POT1a and POT1b, accumulate at telomeres as h

205 A multiprotein complex known as shelterin prevents recognition of telomeric sequences as

206 Shelterin protects chromosome ends, prevents recognition

207 To understand how shelterin protects telomere ends, we investigated the st

208 t protein complex, which is related to human shelterin, protects telomeres from being recognized as D

209 Human telomeres are maintained by the shelterin protein complex in which TRF1 and TRF2 bind di

210 TRF2, a component of the telomere-specific shelterin protein complex, facilitates end protection th

211 east in part, to compromise of the telomeric shelterin protein complex.

212 Telomere uncapping through either TRF2 shelterin protein knockdown or exposure to telomere G-st

213 The reaction mechanism by which the shelterin protein POT1 (Protection of Telomeres 1) unfol

214 ion by Apollo is blocked at both ends by the shelterin protein POT1b.

215 on with telomeres does not require POT1, the shelterin protein that links TPP1 to the single-stranded

216 The shelterin protein TIN2 is required for the telomeric acc

217 We therefore analyzed the central shelterin protein TIN2, which links TPP1/POT1a (and POT1

218 The shelterin protein TPP1 is required for telomere stabilit

219 the N-terminal acidic domain of the telomere shelterin protein TRF1 and demonstrating a novel mechani

220 we show that human RTEL1 interacts with the shelterin protein TRF1, providing a potential recruitmen

221 epair of dysfunctional telomeres lacking the shelterin protein TRF2 by promoting their mobility, thei

222 The shelterin protein TRF2 has come to the limelight for its

223 The shelterin protein TRF2 is essential for chromosome-end p

224 Shelterin protein TRF2 modulates telomere structures by

225 Here, we establish that the shelterin protein TRF2 recruits RTEL1 to telomeres in S

226 Removal of TRF2, a telomere shelterin protein, recapitulates key aspects of telomere

227 t3p is structurally related to the mammalian shelterin protein, TPP1, which also influences telomeras

228 Here we co-express various human shelterin proteins and find that they form defined multi

229 The human shelterin proteins associate with telomeric DNA to confe

230 mere dynamics and measured the expression of shelterin proteins at the transcriptional and translatio

231 accharomyces pombe, interactions between the shelterin proteins Ccq1, Tpz1, and Poz1 are important fo

232 omplexes for their functions, but studies of shelterin proteins have been mostly limited to pairs of

233 rmine the abundance and stoichiometry of the shelterin proteins in the chromatin-bound protein fracti

234 In addition, shelterin proteins play key roles in regulating the recr

235 Mammalian shelterin proteins POT1 and TPP1 form a stable heterodim

236 Shelterin proteins prevent chromosome ends from fusing t

237 The shelterin proteins protect telomeres against activation

238 altered sensitivity to expression changes of shelterin proteins suggesting the mutation causes a defe

239 sponse on depletion of either or both of the shelterin proteins telomeric repeat binding factor 2 (TR

240 Removal of shelterin proteins that protect the 3' overhang in the s

241 AD51, occur without parallel upregulation of shelterin proteins TRF1 and TRF2, and are associated wit

242 er biochemical studies demonstrated that the shelterin proteins TRF1 and TRF2, which preferentially b

243 4 localizes to telomeres and associates with shelterin proteins TRF1 and TRF2.

244 myb-like domain of the same type as in human shelterin proteins TRF1 or TRF2, also possess a histone-

245 telomeric D-loop structures with the help of shelterin proteins TRF1, TRF2, and POT1.

246 Mutations in genes encoding the shelterin proteins TRF1-interacting nuclear factor 2 (TI

247 l features and in vivo effects of individual shelterin proteins, discuss shelterin functions in hemat

248 Pu-27 down-regulates telomeric shelterin proteins, DNA damage response mediators (RAD17

249 omeric DNA is protected and regulated by the shelterin proteins, including the protection of telomere

250 -27 but exhibits no changes in expression of shelterin proteins.

251 es rendered dysfunctional through removal of shelterin proteins.

252 viously observed upon deletion of individual shelterin proteins.

253 old less abundant than their TIN2 partner in shelterin, raising the question of what limits the accum

254 expected 2:1 stoichiometry in the context of shelterin (RAP12:TRF22:TIN21:TPP11:POT11).

255 Extensive data suggest that TRF2 in shelterin remodels telomeres into the t-loop structure,

256 hese results suggest that the DDR induced by shelterin removal does not require substantial telomere

257 Upon shelterin removal, telomeres underwent 53BP1-dependent c

258 equencing), was not substantially altered by shelterin removal.

259 periments, discussed here, have revealed how shelterin represses the ATM and ATR kinase signaling pat

260 large part due to lack of structural data on shelterins, shelterin complex, and its interaction with

261 itional deletion of individual components of shelterin showed that TRF2 was required for the formatio

262 hed work that TIN2/TPP1/POT1 is a functional shelterin subcomplex.

263 e identify a CDK phosphorylation site in the shelterin subunit at Ser365 of TRF2, whose dephosphoryla

264 Elimination of the fission yeast shelterin subunit Ccq1 causes progressive loss of telome

265 he TRF2-interacting factor Rap1, a conserved shelterin subunit of unknown function.

266 unique TINF2 mutations that truncate TIN2, a shelterin subunit that controls telomere length.

267 required to establish telomere cohesion, the shelterin subunit TIN2 and the cohesin subunit SA1.

268 studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres

269 The shelterin subunit Tpz1(TPP1) directly interacts with Ccq

270 Co-depletion of SMCHD1 and the shelterin subunit TRF2 reduced telomeric 3'-overhang rem

271 We show here that a dimer of the shelterin subunit TRF2 wraps approximately 90 bp of DNA

272 Apollo, a nuclease bound to the shelterin subunit TRF2, initiates formation of the 3' ov

273 gh a complex network of interactions between shelterin subunits and telomeric DNA, but not by DNA met

274 mutations that disrupt interactions between shelterin subunits compromise subtelomeric heterochromat

275 tures correlates with reduced association of shelterin subunits Pot1 and Ccq1 at telomeres.

276 on mechanism was suggested recently by which shelterin subunits TRF1, TRF2, and TIN2 mediate telomeri

277 n telomeres, indicating a different fate for shelterin subunits when TIN2 is depleted posttranslation

278 The loss of Taz1 or other Shelterin subunits, including Ccq1 that interacts with C

279 Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and PO

280 o binding sites for Taz1, a component of the Shelterin telomere protection complex.

281 The role of shelterin telomere protection is less understood.

282 -binding factor 2 (TRF2) are two subunits in shelterin that interact with each other.

283 elomeres contain a specific protein complex, shelterin, that functions to protect chromosome ends fro

284 that terminin is the functional analogue of shelterin, the multi-protein complex that protects human

285 n telomeres and interacts with components of shelterin, the protein complex that protects telomeres.

286 Human telomeres bind shelterin, the six-subunit protein complex that protects

287 TRF2 is a component of shelterin, the telomere-specific protein complex that pr

288 uplex binder induces a partial alteration of shelterin through POT1 uncapping from telomeres in human

289 eres of human patients with mutations in the shelterin TIN2.

290 epeats that recruit the multiprotein complex shelterin to build a chromatin structure that protects c

291 bly requires both the recruitment of CLRC by shelterin to chromosome ends and the proper connection o

292 ploys TIN2 and the TPP1/POT1 heterodimers in shelterin to prevent ATR during telomere replication and

293 se access to the telomere, as a component of shelterin, to serving as a processivity factor for telom

294 The duplex telomeric DNA binding factors in shelterin, TRF1 and TRF2, were sufficiently abundant to

295 lomeric DNA and are commonly referred to as "shelterin." We show that in progressive HIV-1 infection,

296 omponent of the telomere maintenance complex shelterin, which is present in species ranging from fiss

297 TPP1 can form a complex called the telosome/shelterin, which is required for telomere protection and

298 sociated with a six-protein complex known as shelterin, which preserves telomere structure and protec

299 eres requires both the enzyme telomerase and shelterin, which protect telomeres from inappropriately

300 is a component of the multiprotein complex "shelterin," which organizes the telomere into a high-ord