TPP1 as a versatile player at the ends of chromosomes
Sijie ZHANG, Zhenhua LUO, Guang SHI, Dan LIU, Zhou SONGYANG, Junjiu HUANG
TPP1 as a versatile player at the ends of chromosomes
Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response (DDR), recombination, and end-to-end fusions, ensuring genome stability. The human telosome/shelterin complex is one of the best-studied telomere-associated protein complexes, made up of six core telomeric proteins TRF1, TRF2, TIN2, RAP1, POT1, and TPP1. TPP1, also known as adrenocortical dysplasia protein homolog (ACD), is a putative mammalian homolog of TEBP-β and belongs to the oligonucleotide binding (OB)-fold-containing protein family. Three functional domains have been identified within TPP1, the N-terminal OB fold, the POT1 binding recruitment domain (RD), and the carboxyl-terminal TIN2-interacting domain (TID). TPP1 can interact with both POT1 and TIN2 to maintain telomere structure, and mediate telomerase recruitment for telomere elongation. These features have indicated TPP1 play an essential role in telomere maintenance. Here, we will review important findings that highlight the functional significance of TPP1, with a focus on its interaction with other telosome components and the telomerase. We will also discuss potential implications in disease therapies.
telomere / TPP1 / TIN2 / telosome/shelterin / telomerase
[1] |
AbreuE, AritonovskaE, ReichenbachP, CristofariG, CulpB, TernsR M, LingnerJ, TernsM P (2010). TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. Mol Cell Biol, 30(12): 2971–2982
CrossRef
Pubmed
Google scholar
|
[2] |
ArmaniosM, BlackburnE H (2012). The telomere syndromes. Nat Rev Genet, 13(10): 693–704
CrossRef
Pubmed
Google scholar
|
[3] |
ArnerićM, LingnerJ (2007). Tel1 kinase and subtelomere-bound Tbf1 mediate preferential elongation of short telomeres by telomerase in yeast. EMBO Rep, 8(11): 1080–1085
CrossRef
Pubmed
Google scholar
|
[4] |
AzzalinC M, ReichenbachP, KhoriauliL, GiulottoE, LingnerJ (2007). Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science, 318(5851): 798–801
CrossRef
Pubmed
Google scholar
|
[5] |
BaumannP, CechT R (2001). Pot1, the putative telomere end-binding protein in fission yeast and humans. Science, 292(5519): 1171–1175
CrossRef
Pubmed
Google scholar
|
[6] |
BilaudT, BrunC, AncelinK, KoeringC E, LarocheT, GilsonE (1997). Telomeric localization of TRF2, a novel human telobox protein. Nat Genet, 17(2): 236–239
CrossRef
Pubmed
Google scholar
|
[7] |
BlackburnE H (2001). Switching and signaling at the telomere. Cell, 106(6): 661–673
CrossRef
Pubmed
Google scholar
|
[8] |
BlascoM A (2005). Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet, 6(8): 611–622
CrossRef
Pubmed
Google scholar
|
[9] |
BlascoM A (2007). Telomere length, stem cells and aging. Nat Chem Biol, 3(10): 640–649
CrossRef
Pubmed
Google scholar
|
[10] |
BryanT M, EnglezouA, GuptaJ, BacchettiS, ReddelR R (1995). Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J, 14(17): 4240–4248
Pubmed
|
[11] |
CarneroA (2010). The PKB/AKT pathway in cancer. Curr Pharm Des, 16(1): 34–44
CrossRef
Pubmed
Google scholar
|
[12] |
CelliG B, de LangeT (2005). DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol, 7(7): 712–718
CrossRef
Pubmed
Google scholar
|
[13] |
CesareA J, ReddelR R (2010). Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet, 11(5): 319–330
CrossRef
Pubmed
Google scholar
|
[14] |
ChawlaR, RedonS, RaftopoulouC, WischnewskiH, GagosS, AzzalinC M (2011). Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. EMBO J, 30(19): 4047–4058
CrossRef
Pubmed
Google scholar
|
[15] |
ChenL Y, LiuD, SongyangZ (2007). Telomere maintenance through spatial control of telomeric proteins. Mol Cell Biol, 27(16): 5898–5909
CrossRef
Pubmed
Google scholar
|
[16] |
ChenL Y, RedonS, LingnerJ (2012a). The human CST complex is a terminator of telomerase activity. Nature, 488(7412): 540–544
CrossRef
Pubmed
Google scholar
|
[17] |
ChenL Y, ZhangY, ZhangQ, LiH, LuoZ, FangH, KimS H, QinL, YotndaP, XuJ, TuB P, BaiY, SongyangZ (2012b). Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol Cell, 47(6): 839–850
CrossRef
Pubmed
Google scholar
|
[18] |
ChenY C, TengS C, WuK J (2009). Phosphorylation of telomeric repeat binding factor 1 (TRF1) by Akt causes telomere shortening. Cancer Invest, 27(1): 24–28
CrossRef
Pubmed
Google scholar
|
[19] |
ChowT T, ZhaoY, MakS S, ShayJ W, WrightW E (2012). Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening. Genes Dev, 26(11): 1167–1178
CrossRef
Pubmed
Google scholar
|
[20] |
ChungJ, KhadkaP, ChungI K (2012). Nuclear import of hTERT requires a bipartite nuclear localization signal and Akt-mediated phosphorylation. J Cell Sci, 125(Pt 11): 2684–2697
CrossRef
Pubmed
Google scholar
|
[21] |
ColginL M, ReddelR R (1999). Telomere maintenance mechanisms and cellular immortalization. Curr Opin Genet Dev, 9(1): 97–103
CrossRef
Pubmed
Google scholar
|
[22] |
CollinsK (2008). Physiological assembly and activity of human telomerase complexes. Mech Ageing Dev, 129(1–2): 91–98
CrossRef
Pubmed
Google scholar
|
[23] |
CollinsK, MitchellJ R (2002). Telomerase in the human organism. Oncogene, 21(4): 564–579
CrossRef
Pubmed
Google scholar
|
[24] |
de LangeT (2002). Protection of mammalian telomeres. Oncogene, 21(4): 532–540
CrossRef
Pubmed
Google scholar
|
[25] |
de LangeT (2004). T-loops and the origin of telomeres. Nat Rev Mol Cell Biol, 5(4): 323–329
CrossRef
Pubmed
Google scholar
|
[26] |
de LangeT (2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev, 19(18): 2100–2110
CrossRef
Pubmed
Google scholar
|
[27] |
DokalI (2011). Dyskeratosis congenita. Hematology (Am Soc Hematol Educ Program), 2011(1): 480–486
CrossRef
Pubmed
Google scholar
|
[28] |
FloresI, CayuelaM L, BlascoM A (2005). Effects of telomerase and telomere length on epidermal stem cell behavior. Science, 309(5738): 1253–1256
CrossRef
Pubmed
Google scholar
|
[29] |
FlynnR L, CentoreR C, O’SullivanR J, RaiR, TseA, SongyangZ, ChangS, KarlsederJ, ZouL (2011). TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature, 471(7339): 532–536
CrossRef
Pubmed
Google scholar
|
[30] |
GrangerM P, WrightW E, ShayJ W (2002). Telomerase in cancer and aging. Crit Rev Oncol Hematol, 41(1): 29–40
CrossRef
Pubmed
Google scholar
|
[31] |
GrayJ T, CelanderD W, PriceC M, CechT R (1991). Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex. Cell, 67(4): 807–814
CrossRef
Pubmed
Google scholar
|
[32] |
GreiderC W, BlackburnE H (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell, 43(2 Pt 1): 405–413
CrossRef
Pubmed
Google scholar
|
[33] |
GreiderC W, BlackburnE H (1989). A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature, 337(6205): 331–337
CrossRef
Pubmed
Google scholar
|
[34] |
GuoX, DengY, LinY, Cosme-BlancoW, ChanS, HeH, YuanG, BrownE J, ChangS (2007). Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. EMBO J, 26(22): 4709–4719
CrossRef
Pubmed
Google scholar
|
[35] |
HaendelerJ, HoffmannJ, RahmanS, ZeiherA M, DimmelerS (2003). Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation. FEBS Lett, 536(1–3): 180–186
CrossRef
Pubmed
Google scholar
|
[36] |
HahnW C, WeinbergR A (2002). Modelling the molecular circuitry of cancer. Nat Rev Cancer, 2(5): 331–341
CrossRef
Pubmed
Google scholar
|
[37] |
HanX, LiuD, ZhangY, LiY, LuW, ChenJ, SongyangZ (2013). Akt regulates TPP1 homodimerization and telomere protection. Aging Cell, 12(6): 1091–1099
|
[38] |
HarleyC B, FutcherA B, GreiderC W (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345(6274): 458–460
CrossRef
Pubmed
Google scholar
|
[39] |
HerbigU, JoblingW A, ChenB P, ChenD J, SedivyJ M (2004). Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell, 14(4): 501–513
CrossRef
Pubmed
Google scholar
|
[40] |
HockemeyerD, DanielsJ P, TakaiH, de LangeT (2006). Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres. Cell, 126(1): 63–77
CrossRef
Pubmed
Google scholar
|
[41] |
HockemeyerD, PalmW, ElseT, DanielsJ P, TakaiK K, YeJ Z, KeeganC E, de LangeT, HammerG D (2007). Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol, 14(8): 754–761
CrossRef
Pubmed
Google scholar
|
[42] |
HoltS E, ShayJ W, WrightW E (1996). Refining the telomere-telomerase hypothesis of aging and cancer. Nat Biotechnol, 14(7): 836–839
CrossRef
Pubmed
Google scholar
|
[43] |
HoughtalingB, CuttonaroL, ChangW, SmithS (2004) A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol, CB14:1621–1631
|
[44] |
HughesT R, EvansS K, WeilbaecherR G, LundbladV (2000). The Est3 protein is a subunit of yeast telomerase. Curr Biol, 10(13): 809–812
CrossRef
Pubmed
Google scholar
|
[45] |
HwangH, BuncherN, OpreskoP, MyongS (2012). POT1–TPP1 regulates telomeric overhang structural dynamics. Structure (London, England: 1993), 20: 1872–1880
|
[46] |
KangS S, KwonT, KwonD Y, DoS I (1999). Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. J Biol Chem, 274(19): 13085–13090
CrossRef
Pubmed
Google scholar
|
[47] |
KarlsederJ, BroccoliD, DaiY, HardyS, de LangeT (1999). p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science, 283(5406): 1321–1325
CrossRef
Pubmed
Google scholar
|
[48] |
KibeT, OsawaG A, KeeganC E, de LangeT (2010). Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol, 30(4): 1059–1066
CrossRef
Pubmed
Google scholar
|
[49] |
KimN W, PiatyszekM A, ProwseK R, HarleyC B, WestM D, HoP L, CovielloG M, WrightW E, WeinrichS L, ShayJ W (1994). Specific association of human telomerase activity with immortal cells and cancer. Science, 266(5193): 2011–2015
CrossRef
Pubmed
Google scholar
|
[50] |
KimS H, KaminkerP, CampisiJ (1999). TIN2, a new regulator of telomere length in human cells. Nat Genet, 23(4): 405–412
CrossRef
Pubmed
Google scholar
|
[51] |
KloetD E, BurgeringB M (2011). The PKB/FOXO switch in aging and cancer. Biochim Biophys Acta, 1813(11): 1926–1937
CrossRef
Pubmed
Google scholar
|
[52] |
LatrickC M, CechT R (2010). POT1-TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation. EMBO J, 29(5): 924–933
CrossRef
Pubmed
Google scholar
|
[53] |
LeS, MooreJ K, HaberJ E, GreiderC W (1999). RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics, 152(1): 143–152
Pubmed
|
[54] |
LeeJ, MandellE K, TuceyT M, MorrisD K, LundbladV (2008). The Est3 protein associates with yeast telomerase through an OB-fold domain. Nat Struct Mol Biol, 15(9): 990–997
CrossRef
Pubmed
Google scholar
|
[55] |
LeeO H, KimH, HeQ, BaekH J, YangD, ChenL Y, LiangJ, ChaeH K, SafariA, LiuD, SongyangZ (2011), Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. Mol Cell Proteomics, 10: M110 001628
|
[56] |
LeiM, PodellE R, CechT R (2004). Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol, 11(12): 1223–1229
CrossRef
Pubmed
Google scholar
|
[57] |
LevyM Z, AllsoppR C, FutcherA B, GreiderC W, HarleyC B (1992). Telomere end-replication problem and cell aging. J Mol Biol, 225(4): 951–960
CrossRef
Pubmed
Google scholar
|
[58] |
LiB, OestreichS, de LangeT (2000). Identification of human Rap1: implications for telomere evolution. Cell, 101(5): 471–483
CrossRef
Pubmed
Google scholar
|
[59] |
LingnerJ, HughesT R, ShevchenkoA, MannM, LundbladV, CechT R (1997). Reverse transcriptase motifs in the catalytic subunit of telomerase. Science, 276(5312): 561–567
CrossRef
Pubmed
Google scholar
|
[60] |
LiuD, O’ConnorM S, QinJ, SongyangZ (2004a). Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem, 279(49): 51338–51342
CrossRef
Pubmed
Google scholar
|
[61] |
LiuD, SafariA, O’ConnorM S, ChanD W, LaegelerA, QinJ, SongyangZ (2004b). PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol, 6(7): 673–680
CrossRef
Pubmed
Google scholar
|
[62] |
LoayzaD, De LangeT (2003). POT1 as a terminal transducer of TRF1 telomere length control. Nature, 423(6943): 1013–1018
CrossRef
Pubmed
Google scholar
|
[63] |
LundbladV, BlackburnE H (1993). An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell, 73(2): 347–360
CrossRef
Pubmed
Google scholar
|
[64] |
ManningB D, CantleyL C (2007). AKT/PKB signaling: navigating downstream. Cell, 129(7): 1261–1274
CrossRef
Pubmed
Google scholar
|
[65] |
MarionR M, StratiK, LiH, TejeraA, SchoeftnerS, OrtegaS, SerranoM, BlascoM A (2009). Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell, 4(2): 141–154
CrossRef
Pubmed
Google scholar
|
[66] |
MaserR S, DePinhoR A (2002). Connecting chromosomes, crisis, and cancer. Science, 297(5581): 565–569
CrossRef
Pubmed
Google scholar
|
[67] |
MoyzisR K, BuckinghamJ M, CramL S, DaniM, DeavenL L, JonesM D, MeyneJ, RatliffR L, WuJ R (1988). A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA, 85(18): 6622–6626
CrossRef
Pubmed
Google scholar
|
[68] |
NandakumarJ, BellC F, WeidenfeldI, ZaugA J, LeinwandL A, CechT R (2012). The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature, 492(7428): 285–289
CrossRef
Pubmed
Google scholar
|
[69] |
NandakumarJ, CechT R (2013). Finding the end: recruitment of telomerase to telomeres. Nat Rev Mol Cell Biol, 14(2): 69–82
CrossRef
Pubmed
Google scholar
|
[70] |
NandakumarJ, PodellE R, CechT R (2010). How telomeric protein POT1 avoids RNA to achieve specificity for single-stranded DNA. Proc Natl Acad Sci USA, 107(2): 651–656
CrossRef
Pubmed
Google scholar
|
[71] |
O’ConnorM S, SafariA, LiuD, QinJ, SongyangZ (2004). The human Rap1 protein complex and modulation of telomere length. J Biol Chem, 279(27): 28585–28591
CrossRef
Pubmed
Google scholar
|
[72] |
O’ConnorM S, SafariA, XinH, LiuD, SongyangZ (2006). A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci USA, 103(32): 11874–11879
CrossRef
Pubmed
Google scholar
|
[73] |
PaeschkeK, JuranekS, SimonssonT, HempelA, RhodesD, LippsH J (2008). Telomerase recruitment by the telomere end binding protein-beta facilitates G-quadruplex DNA unfolding in ciliates. Nat Struct Mol Biol, 15(6): 598–604
CrossRef
Pubmed
Google scholar
|
[74] |
PalmW, de LangeT (2008). How shelterin protects mammalian telomeres. Annu Rev Genet, 42(1): 301–334
CrossRef
Pubmed
Google scholar
|
[75] |
PanierS, DurocherD (2009). Regulatory ubiquitylation in response to DNA double-strand breaks. DNA Repair (Amst), 8(4): 436–443
CrossRef
Pubmed
Google scholar
|
[77] |
QingY F, ZhouJ G, ZhaoM C, XieW G, YangQ B, XingY, ZengS P, JiangH (2012). Altered expression of TPP1 in fibroblast-like synovial cells might be involved in the pathogenesis of rheumatoid arthritis. Rheumatol Int, 32(8): 2503–2510
CrossRef
Pubmed
Google scholar
|
[78] |
RaiR, LiJ M, ZhengH, LokG T, DengY, HuenM S, ChenJ, JinJ, ChangS (2011). The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection. Nat Struct Mol Biol, 18(12): 1400–1407
CrossRef
Pubmed
Google scholar
|
[79] |
RedonS, ReichenbachP, LingnerJ (2007). Protein RNA and protein protein interactions mediate association of human EST1A/SMG6 with telomerase. Nucleic Acids Res, 35(20): 7011–7022
CrossRef
Pubmed
Google scholar
|
[80] |
SaccoA, MourkiotiF, TranR, ChoiJ, LlewellynM, KraftP, ShkreliM, DelpS, PomerantzJ H, ArtandiS E, BlauH M (2010). Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell, 143(7): 1059–1071
CrossRef
Pubmed
Google scholar
|
[81] |
SarperN, ZenginE, KılıçS C (2010). A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex. Pediatr Blood Cancer, 55(6): 1185–1186
CrossRef
Pubmed
Google scholar
|
[82] |
SasaG S, Ribes-ZamoraA, NelsonN D, BertuchA A (2012). Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood. Clin Genet, 81(5): 470–478
CrossRef
Pubmed
Google scholar
|
[83] |
SextonA N, YoumansD T, CollinsK (2012). Specificity requirements for human telomere protein interaction with telomerase holoenzyme. J Biol Chem, 287(41): 34455–34464
CrossRef
Pubmed
Google scholar
|
[84] |
ShilohY (2003). ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer, 3(3): 155–168
CrossRef
Pubmed
Google scholar
|
[85] |
SongyangZ, LiuD (2006). Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres. Crit Rev Eukaryot Gene Expr, 16(2): 103–118
CrossRef
Pubmed
Google scholar
|
[86] |
TalleyJ M, DeZwaanD C, ManessL D, FreemanB C, FriedmanK L (2011). Stimulation of yeast telomerase activity by the ever shorter telomere 3 (Est3) subunit is dependent on direct interaction with the catalytic protein Est2. J Biol Chem, 286(30): 26431–26439
CrossRef
Pubmed
Google scholar
|
[87] |
TaylorD J, PodellE R, TaatjesD J, CechT R (2011). Multiple POT1-TPP1 proteins coat and compact long telomeric single-stranded DNA. J Mol Biol, 410(1): 10–17
CrossRef
Pubmed
Google scholar
|
[88] |
TejeraA M, Stagno d’AlcontresM, ThanasoulaM, MarionR M, MartinezP, LiaoC, FloresJ M, TarsounasM, BlascoM A (2010). TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice. Dev Cell, 18(5): 775–789
CrossRef
Pubmed
Google scholar
|
[89] |
VerdunR E, KarlsederJ (2006). The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell, 127(4): 709–720
CrossRef
Pubmed
Google scholar
|
[90] |
WalneA J, VulliamyT, BeswickR, KirwanM, DokalI (2008). TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood, 112(9): 3594–3600
CrossRef
Pubmed
Google scholar
|
[91] |
WanM, QinJ, SongyangZ, LiuD (2009). OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J Biol Chem, 284(39): 26725–26731
CrossRef
Pubmed
Google scholar
|
[92] |
WangF, PodellE R, ZaugA J, YangY, BaciuP, CechT R, LeiM (2007). The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature, 445(7127): 506–510
CrossRef
Pubmed
Google scholar
|
[93] |
WrightW E, TesmerV M, LiaoM L, ShayJ W (1999). Normal human telomeres are not late replicating. Exp Cell Res, 251(2): 492–499
CrossRef
Pubmed
Google scholar
|
[94] |
WuL, MultaniA S, HeH, Cosme-BlancoW, DengY, DengJ M, BachiloO, PathakS, TaharaH, BaileyS M, DengY, BehringerR R, ChangS (2006). Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell, 126(1): 49–62
CrossRef
Pubmed
Google scholar
|
[95] |
XinH, LiuD, WanM, SafariA, KimH, SunW, O’ConnorM S, SongyangZ (2007). TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature, 445(7127): 559–562
CrossRef
Pubmed
Google scholar
|
[96] |
YangD, HeQ, KimH, MaW, SongyangZ (2011). TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase. J Biol Chem, 286(26): 23022–23030
CrossRef
Pubmed
Google scholar
|
[97] |
YeJ Z, de LangeT (2004). TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Nat Genet, 36(6): 618–623
CrossRef
Pubmed
Google scholar
|
[98] |
YeJ Z, HockemeyerD, KrutchinskyA N, LoayzaD, HooperS M, ChaitB T, de LangeT (2004). POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev, 18(14): 1649–1654
CrossRef
Pubmed
Google scholar
|
[99] |
YenW F, ChicoL, LeiM, LueN F (2011). Telomerase regulatory subunit Est3 in two Candida species physically interacts with the TEN domain of TERT and telomeric DNA. Proc Natl Acad Sci USA, 108(51): 20370–20375
CrossRef
Pubmed
Google scholar
|
[100] |
YuE Y, WangF, LeiM, LueN F (2008). A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3. Nat Struct Mol Biol, 15(9): 985–989
CrossRef
Pubmed
Google scholar
|
[101] |
ZaugA J, CraryS M, Jesse FioravantiM, CampbellK, CechT R (2013). Many disease-associated variants of hTERT retain high telomerase enzymatic activity. Nucleic Acids Res, 41(19): 8969–8978
CrossRef
Pubmed
Google scholar
|
[102] |
ZhangY, ChenL Y, HanX, XieW, KimH, YangD, LiuD, SongyangZ (2013). Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci USA, 110(14): 5457–5462
CrossRef
Pubmed
Google scholar
|
[103] |
ZhaoY, SfeirA J, ZouY, BusemanC M, ChowT T, ShayJ W, WrightW E (2009). Telomere extension occurs at most chromosome ends and is uncoupled from fill-in in human cancer cells. Cell, 138(3): 463–475
CrossRef
Pubmed
Google scholar
|
[104] |
ZhongF, SavageS A, ShkreliM, GiriN, JessopL, MyersT, ChenR, AlterB P, ArtandiS E (2011). Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita. Genes Dev, 25(1): 11–16
CrossRef
Pubmed
Google scholar
|
[105] |
ZhongF L, BatistaL F, FreundA, PechM F, VenteicherA S, ArtandiS E (2012). TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell, 150(3): 481–494
CrossRef
Pubmed
Google scholar
|
[106] |
ZhongZ, ShiueL, KaplanS, de LangeT (1992). A mammalian factor that binds telomeric TTAGGG repeats in vitro. Mol Cell Biol, 12(11): 4834–4843
Pubmed
|
/
〈 | 〉 |