Telomerase enzymatic component hTERT shortens long telomeres in human cells

Cell Cycle

Volumn 13, Issue 11, 2014, Pages 1765-1776

  Zheng, Yun Ling ^a   Zhang, Fan ^b   Sun, Bing ^a   Du, Juan ^b   Sun, Chongkui ^b   Yuan, Jie ^c   Wang, Ying ^a   Tao, Lian ^a   Kota, Krishna ^a   Liu, Xuefeng ^a   Schlegel, Richard ^a   Yang, Qin ^b  

^a GEORGETOWN UNIVERSITY   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MEDICAL COLLEGE OF JINAN UNIVERSITY   (China)

Author keywords

hTERT; hTR; Length regulation; Telomerase; Telomere length upper limit; Telomeres; TPP1

Indexed keywords

CIRCULAR DNA; PROTEIN; SHELTERIN PROTEIN TPP1; TELOMERASE; TELOMERASE REVERSE TRANSCRIPTASE; UNCLASSIFIED DRUG; ACD PROTEIN, HUMAN; SHELTERIN, HUMAN; TELOMERE BINDING PROTEIN; TERT PROTEIN, HUMAN;

ARTICLE; CANCER CELL; CANCER CELL LINE; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVITY; EPITHELIUM CELL; FIBROBLAST; HUMAN; HUMAN CELL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; TELOMERE DYSFUNCTION; TELOMERE HOMEOSTASIS; TELOMERE SHORTENING; UPREGULATION; CHROMOSOME ANALYSIS; FLUORESCENCE IN SITU HYBRIDIZATION; FLUORESCENT ANTIBODY TECHNIQUE; GENETICS; IMMUNOPRECIPITATION; METABOLISM; PHYSIOLOGY; TWO DIMENSIONAL GEL ELECTROPHORESIS; WESTERN BLOTTING;

BLOTTING, WESTERN; CYTOGENETIC ANALYSIS; DNA, CIRCULAR; ELECTROPHORESIS, GEL, TWO-DIMENSIONAL; FIBROBLASTS; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMMUNOPRECIPITATION; IN SITU HYBRIDIZATION, FLUORESCENCE; TELOMERASE; TELOMERE SHORTENING; TELOMERE-BINDING PROTEINS;

EID: 84901787515     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.28705     Document Type: Article

References (60)

1. Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106:661-73; PMID:11572773; http://dx.doi.org/10.1016/S0092-8674(01)00492-5
2. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43:405-13; PMID:3907856; http://dx.doi.org/10.1016/0092-8674(85)90170-9
3. Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 1989; 337:331-7; PMID:2463488; http://dx.doi.org/10.1038/337331a0
4. Greider CW. Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci U S A 1998; 95:90-2; PMID:9419332; http://dx.doi.org/10.1073/pnas. 95.1.90
5. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43:405-13; PMID:3907856; http://dx.doi.org/10.1016/0092-8674(85)90170-9
6. Murnane JP, Sabatier L, Marder BA, Morgan WF. Telomere dynamics in an immortal human cell line. EMBO J 1994; 13:4953-62; PMID:7957062
7. Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 1997; 3:1271-4; PMID:9359704; http://dx.doi.org/10.1038/nm1197-1271
8. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 1995; 14:4240-8; PMID:7556065
9. Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet 2010; 11:319-30; PMID:20351727; http://dx.doi.org/10.1038/nrg2763
10. Lustig AJ. Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion. Nat Rev Genet 2003; 4:916-23; PMID:14634639; http://dx.doi.org/10.1038/nrg1207
11. Pickett HA, Cesare AJ, Johnston RL, Neumann AA, Reddel RR. Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO J 2009; 28:799-809; PMID:19214183; http://dx.doi.org/10.1038/emboj.2009.42
12. Pickett HA, Henson JD, Au AY, Neumann AA, Reddel RR. Normal mammalian cells negatively regulate telomere length by telomere trimming. Hum Mol Genet 2011; 20:4684-92; PMID:21903669; http://dx.doi.org/10.1093/hmg/ddr402
13. Wang RC, Smogorzewska A, de Lange T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 2004; 119:355-68; PMID:15507207; http://dx.doi.org/10.1016/j.cell.2004.10.011
14. Zheng YL, Zhou X, Loffredo CA, Shields PG, Sun B. Telomere deficiencies on chromosomes 9p, 15p, 15q and Xp: potential biomarkers for breast cancer risk. Hum Mol Genet 2011; 20:378-86; PMID:20956286; http://dx.doi.org/10.1093/hmg/ ddq461
15. Liu X, Ory V, Chapman S, Yuan H, Albanese C, Kallakury B, Timofeeva OA, Nealon C, Dakic A, Simic V, et al. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am J Pathol 2012; 180:599-607; PMID:22189618; http://dx.doi.org/10.1016/j.ajpath.2011.10.036
16. Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA. Inhibition of telomerase limits the growth of human cancer cells. Nat Med 1999; 5:1164-70; PMID:10502820; http://dx.doi.org/10.1038/13495
17. Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, DeCaprio JA, et al. Telomerase maintains telomere structure in normal human cells. Cell 2003; 114:241-53; PMID:12887925; http://dx.doi.org/10.1016/S0092-8674(03)00550-6
18. Latrick CM, Cech TR. POT1-TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation. EMBO J 2010; 29:924-33; PMID:20094033; http://dx.doi.org/10.1038/emboj.2009.409
19. Zaug AJ, Podell ER, Nandakumar J, Cech TR. Functional interaction between telomere protein TPP1 and telomerase. Genes Dev 2010; 24:613-22; PMID:20231318; http://dx.doi.org/10.1101/gad.1881810
20. Nandakumar J, Bell CF, Weidenfeld I, Zaug AJ, Leinwand LA, Cech TR. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature 2012; 492:285-9; PMID:23103865; http://dx.doi.org/10.1038/ nature11648
21. Nandakumar J, Cech TR. Finding the end: recruitment of telomerase to telomeres. Nat Rev Mol Cell Biol 2013; 14:69-82; PMID:23299958; http://dx.doi.org/10.1038/nrm3505
22. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature 2007; 445:506-10; PMID:17237768; http://dx.doi.org/10.1038/nature05454
23. Zhong FL, Batista LF, Freund A, Pech MF, Venteicher AS, Artandi SE. TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell 2012; 150:481-94; PMID:22863003; http://dx.doi.org/10. 1016/j.cell.2012.07.012
24. Zeng S, Xiang T, Pandita TK, Gonzalez-Suarez I, Gonzalo S, Harris CC, Yang Q. Telomere recombination requires the MUS81 endonuclease. Nat Cell Biol 2009; 11:616-23; PMID:19363487; http://dx.doi.org/10.1038/ncb1867
25. Zeng S, Yang Q. The MUS81 endonuclease is essential for telomerase negative cell proliferation. Cell Cycle 2009; 8:2157-60; PMID:19617716; http://dx.doi.org/10.4161/cc.8.14.9149
26. Cesare AJ, Griffith JD. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol Cell Biol 2004; 24:9948-57; PMID:15509797; http://dx.doi.org/10.1128/MCB.24.22.9948-9957.2004
27. Yang Q. Cellular senescence, telomere recombination and maintenance. Cytogenet Genome Res 2008; 122:211-8; PMID:19188689; http://dx.doi.org/10.1159/ 000167806
28. Reddel RR. Alternative lengthening of telomeres, telomerase, and cancer. Cancer Lett 2003; 194:155-62; PMID:12757973; http://dx.doi.org/10.1016/S0304- 3835(02)00702-4
29. Blackburn EH. Telomere states and cell fates. Nature 2000; 408:53-6; PMID:11081503; http://dx.doi.org/10.1038/35040500
30. Lue NF, Yu EY, Lei M. A popular engagement at the ends. Nat Struct Mol Biol 2013; 20:10-2; PMID:23288360; http://dx.doi.org/10.1038/nsmb.2483
31. Lue NF. Closing the feedback loop: how cells "count" telomere-bound proteins. Mol Cell 2009; 33:413-4; PMID:19250901; http://dx.doi.org/10.1016/j.molcel.2009.02.001
32. Sharma GG, Gupta A, Wang H, Scherthan H, Dhar S, Gandhi V, Iliakis G, Shay JW, Young CS, Pandita TK. hTERT associates with human telomeres and enhances genomic stability and DNA repair. Oncogene 2003; 22:131-46; PMID:12527915; http://dx.doi.org/10.1038/sj.onc.1206063
33. Sharma GG, Hwang KK, Pandita RK, Gupta A, Dhar S, Parenteau J, Agarwal M, Worman HJ, Wellinger RJ, Pandita TK. Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation. Mol Cell Biol 2003; 23:8363-76; PMID:14585993; http://dx.doi.org/10.1128/MCB.23.22. 8363-8376.2003
34. Pandita TK. ATM function and telomere stability. Oncogene 2002; 21:611-8; PMID:11850786; http://dx.doi.org/10.1038/sj.onc.1205060
35. Wood LD, Halvorsen TL, Dhar S, Baur JA, Pandita RK, Wright WE, Hande MP, Calaf G, Hei TK, Levine F, et al. Characterization of ataxia telangiectasia fibroblasts with extended life-span through telomerase expression. Oncogene 2001; 20:278-88; PMID:11313956; http://dx.doi.org/10.1038/sj.onc.1204072
36. Wan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EY, et al. SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. Cell Rep 2013; 4:861-9; PMID:24012755; http://dx.doi.org/10.1016/j.celrep.2013.08.017
37. Pfeiffer V, Lingner J. TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends. PLoS Genet 2012; 8:e1002747; PMID:22719262; http://dx.doi.org/10.1371/journal.pgen.1002747
38. Oulton R, Harrington L. A human telomerase-associated nuclease. Mol Biol Cell 2004; 15:3244-56; PMID:15121883; http://dx.doi.org/10.1091/mbc.E04-03-0178
39. Pandita TK, Hunt CR, Sharma GG, Yang Q. Regulation of telomere movement by telomere chromatin structure. Cell Mol Life Sci 2007; 64:131-8; PMID:17219023; http://dx.doi.org/10.1007/s00018-006-6465-0
40. Teixeira MT, Arneric M, Sperisen P, Lingner J. Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 2004; 117:323-35; PMID:15109493; http://dx.doi.org/10.1016/S0092-8674(04)00334-4
41. D'Souza Y, Chu TW, Autexier C. A translocation-defective telomerase with low levels of activity and processivity stabilizes short telomeres and confers immortalization. Mol Biol Cell 2013; 24:1469-79; PMID:23447707; http://dx.doi.org/10.1091/mbc.E12-12-0889
42. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345:458-60; PMID:2342578; http://dx.doi.org/10. 1038/345458a0
43. Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 1973; 41:181-90; PMID:4754905; http://dx.doi.org/ 10.1016/0022-5193(73)90198-7
44. Watson JD. Origin of concatemeric T7 DNA. Nat New Biol 1972; 239:197-201; PMID:4507727; http://dx.doi.org/10.1038/newbio239197a0
45. Krizhanovsky V, Xue W, Zender L, Yon M, Hernando E, Lowe SW. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb Symp Quant Biol 2008; 73:513-22; PMID:19150958; http://dx.doi.org/10.1101/sqb.2008.73.048
46. Harley CB. Telomere loss: mitotic clock or genetic time bomb? Mutat Res 1991; 256:271-82; PMID:1722017; http://dx.doi.org/10.1016/0921-8734(91)90018-7
47. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345:458-60; PMID:2342578; http://dx.doi.org/10. 1038/345458a0
48. de Lange T. Telomeres and senescence: ending the debate. Science 1998; 279:334-5; PMID:9454329; http://dx.doi.org/10.1126/science.279.5349.334
49. Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 1992; 11:1921-9; PMID:1582420
50. Counter CM, Botelho FM, Wang P, Harley CB, Bacchetti S. Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes. J Virol 1994; 68:3410-4; PMID:8151802
51. Engelhardt M, Drullinsky P, Guillem J, Moore MA. Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin Cancer Res 1997; 3:1931-41; PMID:9815582
52. Calado RT, Young NS. Telomere diseases. N Engl J Med 2009; 361:2353-65; PMID:20007561; http://dx.doi.org/10.1056/NEJMra0903373
53. Prescott J, Wentzensen IM, Savage SA, De V. I. Epidemiologic evidence for a role of telomere dysfunction in cancer etiology. Mutat Res 2012; 730:75-84; PMID:21756922
54. Zhu H, Belcher M, van der Harst P. Healthy aging and disease: role for telomere biology? Clin Sci (Lond) 2011; 120:427-40; PMID:21271986; http://dx.doi.org/10.1042/CS20100385
55. Sanders JL, Fitzpatrick AL, Boudreau RM, et al. Leukocyte Telomere Length Is Associated With Noninvasively Measured Age-Related Disease: The Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci 2012; 67:409-16; PMID:21934123
56. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008; 8:167-79; PMID:18256617; http://dx.doi.org/10.1038/nrc2275
57. Yang Q, Zheng YL, Harris CC. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol Cell Biol 2005; 25:1070-80; PMID:15657433; http://dx.doi.org/10.1128/MCB.25.3.1070-1080.2005
58. Jiang WQ, Zhong ZH, Henson JD, Reddel RR. Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene 2007; 26:4635-47; PMID:17297460; http://dx.doi.org/10. 1038/sj.onc.1210260
59. Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered telomere state, not telomere loss. Science 2002; 295:2446-9; PMID:11923537; http://dx.doi.org/10.1126/science.1069523
60. Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003; 300:1542-8; PMID:12791985; http://dx.doi.org/10.1126/science.1083430