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Many ways to telomere dysfunction: in vivo studies using mouse models

Oncogene volume 21, pages 584–591 (2002)Cite this article

Abstract

The existence of a capping structure at the extremities of chromosomes was first deduced in the 1930s by Herman Müller (Müller, 1938), who showed that X-irradiation of Drosophila rarely resulted in terminal deletions or inversions of chromosomes, suggesting that chromosome ends have protective structures that distinguish them from broken chromosomes, which he named telomeres. In this review, we will focus on mammalian telomeres and, in particular, on the analysis of different mouse models for proteins that are important for telomere function, such as telomerase and various telomere-binding proteins. These murine models are helping us to understand the consequences of telomere dysfunction for cancer, aging and DNA repair, as well as, the molecular mechanisms by which telomeres exert their protective function.

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References

  • Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA . 2000 Nature 406: 641–645

  • Bailey SM, Meyne J, Chen DJ, Kurimasa A, Li GC, Lehnert BE, Goodwin EH . 1999 Proc. Natl. Acad. Sci. USA 96: 14899–14904

  • Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y . 1998 Science 281: 1674–1677

  • Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A . 1996 Cell 86: 159–171

  • Barlow C, Brown KD, Deng CX, Tagle DA, Wynshaw-Borris A . 1997 Nature Genet. 17: 453–456

  • Baumann P, Cech TR . 2001 Science 292: 1171–1175

  • Bianchi A, de Lange T . 1999 J. Biol. Chem. 274: 21223–21227

  • Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E . 1997 Nat. Genet. 17: 236–239

  • Blackburn EH . 2000 Nature 408: 53–56

  • Blasco MA, Funk WD, Villeponteau B, Greider CW . 1995 Science 269: 1267–1270

  • Blasco MA, Gasser SM, Lingner J . 1999 Genes Dev. 13: 2353–2359

  • Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW . 1997 Cell 91: 25–34

  • Boulton SJ, Jackson SP . 1996 Nucleic. Acids Res. 24: 4639–4648

  • Boulton SJ, Jackson SP . 1998 EMBO J. 17: 1819–1828

  • Broccoli D, Smogorzewska A, Chong L, de Lange T . 1997 Nat. Genet. 17: 231–235

  • Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR . 1997 Nat. Med. 3: 1271–1274

  • Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR . 1995 EMBO J. 14: 4240–4248

  • Bürkle A, Schreiber V, Dantzer F, Oliver FJ, Niedergang C, de Murcia G, Ménissier de Murcia J . 2000 From DNA damage and stress signaling to cell death. Poly ADP-ribosylation reactions de Murcia G and Shall S (eds) Oxford University Press, Oxford pp 80–124

    Google Scholar 

  • Chen Q, Ijpma A, Greider CW . 2001 Mol. Cell. Biol. 21: 1819–1827

  • Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA . 1999 Cell 97: 527–538

  • Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempst P, de Lange T . 1995 Science 270: 1663–1667

  • Cohen H, Sinclair DA . 2001 Proc. Natl. Acad. Sci. USA 98: 3174–3179

  • Collins K . 2000 Curr. Opin. Cell Biol. 12: 378–383

  • d'Adda di Fagagna F, Hande MP, Tong WM, Lansdorp PM, Wang ZQ, Jackson SP . 1999 Nat. Genet. 23: 76–80

  • de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, Varmus HE . 1990 Mol. Cell. Biol. 10: 518–527

  • de Lange T . 2001 Science 292: 1171–1175

  • Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, Ried T, Nussenzweig A . 2000 Nature 404: 510–514

  • Dunham MA, Neumann AA, Fasching CL, Reddel RR . 2000 Nat. Genet. 26: 447–450

  • Gonzalez-Suarez E, Samper E, Flores JM, Blasco MA . 2000 Nat. Genet. 26: 114–117

  • Gonzalez-Suarez E, Samper E, Ramirez A, Flores JM, Martin-Caballero J, Jorcano JL, Blasco MA . 2001 EMBO J. 20: 2619–2630

  • Goytisolo FA, Samper E, Edmonson S, Taccioli GE, Blasco MA . 2001 Mol. Cell. Biol. 21: 3642–3651

  • Goytisolo FA, Samper E, Martin-Caballero J, Finnon P, Herrera E, Flores JM, Bouffler SD, Blasco MA . 2000 J. Exp. Med. 192: 1625–1636

  • Gravel S, Larrivee M, Labrecque P, Wellinger RJ . 1998 Science 280: 741–744

  • Greenberg RA, Chin L, Femino A, Lee KH, Gottlieb GJ, Singer RH, Greider CW, DePinho RA . 1999 Cell 97: 515–525

  • Greider CW . 1999 Cell 97: 419–422

  • Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T . 1999 Cell 97: 503–514

  • Guarente L . 1997 Science 275: 943–944

  • Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA . 1999 Nature Med. 5: 1164–1170

  • Hande MP, Samper E, Lansdorp P, Blasco MA . 1999a J. Cell. Biol. 144: 589–601

  • Hande P, Slijepcevic P, Silver A, Bouffler S, van Buul P, Bryant P, Lansdorp P . 1999b Genomics 56: 221–223

  • Hande MP, Balajee AS, Tchirkov A, Wynshaw-Boris A, Lansdorp P. M . 2001 Hum. Mol. Genet. 10: 519–528

  • Harley CB, Futcher AB, Greider CW . 1990 Nature 345: 458–460

  • Hemann MT, Greider CW . 1999 Nucl. Acids. Res. 27: 3964–3969

  • Hemann MT, Greider CW . 2000 Nucleic. Acids Res. 28: 4474–4478

  • Herrera E, Martinez AC, Blasco MA . 2000 EMBO J. 19: 472–481

  • Herrera E, Samper E, Blasco MA . 1999a EMBO J. 18: 1172–1181

  • Herrera E, Samper E, Martin-Caballero J, Flores JM, Lee HW, Blasco MA . 1999b EMBO J. 18: 2950–2960

  • Hsu HL, Gilley D, Blackburn EH, Chen DJ . 1999 Proc. Natl. Acad. Sci. USA 96: 12454–12458

  • Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ . 2000 Genes Dev. 14: 2807–2812

  • Huang P, Pryde FE, Lester D, Maddison RL, Borts RH, Hickson ID, Louis EJ . 2001 Curr. Biol. 11: 125–129

  • Johnson FB, Marciniak RA, McVey M, Stewart SA, Hahn WC, Guarente L . 2001 EMBO J. 20: 905–913

  • Kaminker PG, Kim SH, Taylor RD, Zebarjadian Y, Funk WD, Morin GB, Yaswen P, Campisi J . 2001 J. Biol. Chem. 276: 35891–35899

  • Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T . 1999 Science 283: 1321–1325

  • Kim SH, Kaminker P, Campisi J . 1999 Nat. Genet. 23: 405–412

  • Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM . 1995 Science 267: 1178–1183

  • Laroche T, Martin SG, Gotta M, Gorham HC, Pryde FE, Louis EJ, Gasser SM . 1998 Curr. Biol. 8: 653–656

  • Le S, Moore JK, Haber JE, Greider CW . 1999 Genetics 152: 143–152

  • Lee HW, Blasco MA, Gottlieb GJ, Horner JW, Greider CW, DePinho RA . 1998 Nature 392: 569–574

  • Lee KH, Rudolph KL, Ju YJ, Greenberg RA, Cannizzaro L, Chin L, Weiler SR, DePinho RA . 2001 Proc. Natl. Acad. Sci. USA 98: 3381–3386

  • Li B, Oestreich S, de Lange T . 2000 Cell 101: 471–483

  • Liu Y, Snow BE, Hande MP, Yeung D, Erdmann NJ, Wakeham A, Itie A, Siderovski DP, Lansdorp PM, Robinson MO, Harrington L . 2000 Curr. Biol. 10: 1459–1462

  • Lundblad V, Blackburn EH . 1993 Cell 73: 347–360

  • Luo G, Yao MS, Bender CF, Mills M, Bladl AR, Bradley A, Petrini JH . 1999 Proc. Natl. Acad. Sci. USA 96: 7376–7381

  • McElligott R, Wellinger RJ . 1997 EMBO J. 16: 3705–3714

  • Ménissier de Murcia J, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M, Oliver FJ, Masson M, Dierich A, LeMeur M, Walztinger C, Chambon P, de Murcia G . 1997 Proc. Natl. Acad. Sci. USA 94: 7303–7307

  • Metcalfe JA, Parkhill J, Campbell L, Stacey M, Biggs P, Byrd PJ, Taylor AM . 1996 Nat. Genet. 13: 350–353

  • Müller HJ . 1938 Collect. Net. Woods Hole 13: 181–198

  • Naito T, Matsuura A, Ishikawa F . 1998 Nat. Genet. 20: 203–206

  • Niida H, Matsumoto T, Satoh H, Shiwa M, Tokutake Y, Furuichi Y, Shinkai Y . 1998 Nat. Genet. 19: 203–206

  • Nikaido R, Haruyama T, Watanabe Y, Iwata H, Iida M, Sugimura H, Yamada N, Ishikawa F . 1999 Genes Cells 4: 563–572

  • Nugent CI, Lundblad V . 1998a Genes Dev. 12: 1073–1085

  • Nugent CI, Bosco G, Ross LO, Evans SK, Salinger AP, Moore JK, Haber JE, Lundblad V . 1998b Curr. Biol. 8: 657–660

  • Nussenzweig A, Chen C, da Costa Soares V, Sanchez M, Sokol K, Nussenzweig MC, Li GC . 1996 Nature 382: 551–555

  • Ohki R, Tsurimoto T, Ishikawa F . 2001 Mol. Cell. Biol. 21: 5753–5766

  • Pandita TK, Pathak S, Geard CR . 1995 Cytogenet. Cell Genet. 71: 86–93

  • Rizki A, Lundblad V . 2001 Nature 411: 713–716

  • Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA . 1999 Cell 96: 701–712

  • Rudolph KL, Millard M, Bosenberg MW, DePinho RA . 2001 Nat. Genet. 28: 155–159

  • Samper E, Goytisolo FA, Menissier-de Murcia J, Gonzalez-Suarez E, Cigudosa JC, de Murcia G, Blasco MA . 2001a J. Cell. Biol. 154: 49–60

  • Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA . 2000 EMBO Reports 1: 244–252

  • Samper E, Flores JM, Blasco MA . 2001b EMBO Reports 2: 1–8

  • Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA . 1996 Cell 85: 27–37

  • Shay JW, Bacchetti S . 1997 Eur. J. Cancer 33: 787–791

  • Shiloh Y . 1995 Eur. J. Hum. Genet. 3: 116–138

  • Smilenov LB, Morgan SE, Mellado W, Sawant SG, Kastan MB, Pandita TK . 1997 Oncogene 15: 2659–2665

  • Smith GC, Jackson SP . 1999 Genes Dev. 13: 916–934

  • Smith S, de Lange T . 2000 Curr. Biol. 10: 1299–1302

  • Smith S, Giriat I, Schmitt A, de Lange T . 1998 Science 282: 1484–1487

  • Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T . 2000 Mol. Cell. Biol. 20: 1659–1668

  • Song K, Jung D, Jung Y, Lee SG, Lee I . 2000 FEBS Lett. 481: 81–85

  • Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF . 1992 Science 256: 668–670

  • Taccioli GE, Amatucci AG, Beamish HJ, Gell D, Xiang XH, Torres Arzayus MI, Priestley A, Jackson SP, Marshak Rothstein A, Jeggo PA, Herrera VL . 1998 Immunity 9: 355–366

  • van Steensel B, de Lange T . 1997 Nature 385: 676–677

  • van Steensel B, Smogorzewska A, de Lange T . 1998 Cell 92: 401–413

  • Vogel H, Lim DS, Karsenty G, Finegold M, Hasty P . 1999 Proc. Natl. Acad. Sci. USA 96: 10770–10775

  • Wang ZQ, Auer B, Stingl L, Berghammer H, Haidacher D, Schweiger M, Wagner EF . 1995 Genes Dev. 9: 509–520

  • Wong KK, Chang S, Weiler SR, Ganesan S, Chaudhuri J, Zhu C, Artandi SE, Rudolph KL, Gottlieb GJ, Chin L, Alt FW, DePinho RA . 2000 Nat. Genet. 26: 85–88

  • Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW . 1997 Genes Dev. 11: 2801–2809

  • Wu L, Hickson ID . 2001 Science 292: 229–230

  • Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RG, Kipling D . 2000 Nat. Genet. 24: 16–17

  • Xiao Y, Weaver DT . 1997 Nucleic. Acids Res. 25: 2985–2991

  • Yankiwski V, Marciniak RA, Guarente L, Neff NF . 2000 Proc. Natl. Acad. Sci. USA 97: 5214–5219

  • Zhang X, Mar V, Zhou W, Harrington L, Robinson MO . 1999 Genes Dev. 13: 2388–2399

  • Zhu CM, Bogue MA, Lim DS, Hasty P, Roth DB . 1996 Cell 86: 379–389

  • Zhu XD, Kuster B, Mann M, Petrini JH, Lange T . 2000 Nat. Genet. 25: 347–352

  • Zhu J, Petersen S, Tessarollo L, Nussenzweig A . 2001 Curr. Biol. 11: 105–109

  • Zijlmans JM, Martens UM, Poon SS, Raap AK, Tanke HJ, Ward RK, Lansdorp PM . 1997 Proc. Natl. Acad. Sci. USA 94: 7423–7428

  • Zumstein LA, Lundblad V . 1999 Nature Med. 5: 1129–1130

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Acknowledgements

We thank Manuel Serrano for helpful comments. Research at the laboratory of MA Blasco is funded by Swiss Bridge Award 2000, by grants PM97-0133 from the Ministry of Science and Technology (MCT), Spain, and by grants FIGH-CT1999-00009, FIGH-CT-1999-00002 and QLG1-1999-01341, from the EU, and by the Department of Immunology and Oncology (DIO). The DIO was founded and is supported by the Spanish Research Council (CSIC) and by the Pharmacia Corporation.

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  1. Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, Madrid, E-28049, Spain

    Fermín A Goytisolo & María A Blasco

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Correspondence to María A Blasco.

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Goytisolo, F., Blasco, M. Many ways to telomere dysfunction: in vivo studies using mouse models. Oncogene 21, 584–591 (2002). https://doi.org/10.1038/sj.onc.1205085

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