ライフサイエンスコーパス: shelterin

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

2 ificantly to the end protection functions of shelterin.

3 hinery that form a protective complex termed shelterin.

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

5 e the functional compartmentalization within shelterin.

6 ish whether TPP1 has additional functions in shelterin.

7 heterodimers that bind to other proteins in shelterin.

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

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

10 tectable effect on other components of mouse shelterin.

11 and cohesin, I will refer to this complex as shelterin.

12 architecturally and functionally similar to shelterin.

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

14 ains elusive due to the diverse functions of shelterin.

15 ological tools to investigate the biology of shelterin.

16 g additional protection against resection by shelterin.

17 ter of which results in the complete loss 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 cates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senesc

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

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

42 operativity as a conserved driving force for shelterin assembly.

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

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

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

46 How does shelterin avert these events?

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

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

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

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

58 The Shelterin complex associates with telomeres and plays an

59 The conserved multifunctional shelterin complex associates with telomeres to coordinat

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

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

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

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

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

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

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

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

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

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

70 The shelterin complex is a macromolecular assembly of protei

71 The conserved shelterin complex is critical for chromosome capping and

72 Evolutionarily conserved shelterin complex is essential for telomere maintenance

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

74 The shelterin complex plays dual functions in telomere homeo

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

99 omeric DNA repeats bound by the multiprotein shelterin complex.

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

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

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

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

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

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

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

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

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

109 1(ATM)/Rad3(ATR)-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved

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

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

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

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

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

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

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

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

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

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

120 The telomeric shelterin component TPP1 has critical functions in telom

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

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

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

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

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

126 icient duplication of telomeres requires the shelterin component TRF1.

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

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

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

130 Shelterin component TRF2 prevents ATM activation, while

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

152 mposed of telomeric repeats is recognized by shelterin components.

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

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

155 Shelterin contains two closely related proteins (TRF1 an

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

157 3' overhang formation is thus a multistep, shelterin-controlled process, ensuring functional telome

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

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

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

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

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

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

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

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

166 The shelterin-free telomeres are processed by microhomology-

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

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

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

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

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

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

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

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

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

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

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

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

179 Shelterin includes the heterodimeric POT1-TPP1 protein,

180 1 is more extensive upon complete removal of shelterin, indicating additional protection against rese

181 Shelterin is an essential telomeric protein complex that

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

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

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

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

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

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

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

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

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

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

192 ing rescued heterochromatin defects in these shelterin mutants.

193 Although many shelterin mutations affect subtelomeric heterochromatin

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

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

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

197 Shelterin protects chromosome ends, prevents recognition

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

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

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

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

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

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

204 The shelterin protein TIN2 is required for the telomeric acc

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

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

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

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

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

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

211 Shelterin protein TRF2 modulates telomere structures by

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

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

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

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

216 The human shelterin proteins associate with telomeric DNA to confe

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

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

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

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

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

222 Mammalian shelterin proteins POT1 and TPP1 form a stable heterodim

223 Shelterin proteins prevent chromosome ends from fusing t

224 The shelterin proteins protect telomeres against activation

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

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

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

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

229 4 localizes to telomeres and associates with shelterin proteins TRF1 and TRF2.

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

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

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

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

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

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

236 They are interconnected by three additional shelterin proteins, TIN2, TPP1, and Rap1, forming a comp

237 -27 but exhibits no changes in expression of shelterin proteins.

238 es rendered dysfunctional through removal of shelterin proteins.

239 viously observed upon deletion of individual shelterin proteins.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

257 mutations that disrupt interactions between shelterin subunits compromise subtelomeric heterochromat

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

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

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

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

262 Three shelterin subunits, TRF1, TRF2, and POT1 directly recogn

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

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

265 The role of shelterin telomere protection is less understood.

266 Without the protective activity of shelterin, telomeres are no longer hidden from the DNA d

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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