Mice with bad ends: Mouse models for the study of telomeres and telomerase in cancer and aging

EMBO Journal

Volumn 24, Issue 6, 2005, Pages 1095-1103

  Blasco, María A ^a  

^a Centro Nacional de Investigaciones Oncológicas   (Spain)

Author keywords

Aging; Cancer; Mouse; Telomerase; Telomeres

Indexed keywords

REPETITIVE DNA; TELOMERASE; TELOMERE BINDING PROTEIN;

AGING; CANCER; CHROMATIN; CHROMOSOME; DNA DAMAGE; DNA MODIFICATION; ENZYME ACTIVITY; EPIGENETICS; EUKARYOTE; HETEROCHROMATIN; HUMAN; MOUSE; MUTANT; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; TELOMERE;

AGING; ANIMALS; CHROMATIN; DISEASE MODELS, ANIMAL; EPIGENESIS, GENETIC; HUMANS; MICE; MODELS, ANIMAL; NEOPLASMS; TELOMERASE; TELOMERE;

EUKARYOTA;

EID: 17144420804     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.emboj.7600598     Document Type: Review

References (117)

1. Artandi SE, Alson S, Tietze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD, DePinho RA (2002) Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci USA 99: 8191-8196
2. Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA (2000) Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406: 641-645
3. Bailey SM, Conforth MN, Kurimasa A, Chen DJ, Goodwin EH (2001) Strand-specific postreplicative processing of mammalian telomeres. Science 293: 2462-2465
4. Bailey SM, Cornforth MN, Ullrich RL, Goodwin EH (2004) Dysfunctional mammalian telomeres join with DNA double-strand breaks. DNA Repair 3: 349-357
5. Bailey SM, Meyne J, Chen DJ, Kurimasa A, Li GC, Lehnert BE, Goodwin EH (1999) DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc Natl Acad Sci USA 96: 14899-14904
6. Baumann P, Cech TR (2001) Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292: 1171-1175
7. Baur JA, Zou Y, Shay JW, Wright WE (2001) Telomere position effect in human cells. Science 292: 2075-2077
8. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E (1997) Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 17: 236-239
9. Blackburn EH (2001) Switching and signaling at the telomere. Cell 106: 661-673
10. Blasco MA (2002) Telomerase beyond telomeres. Nat Rev Cancer 2: 627-632
11. Blasco MA, Funk WD, Villeponteau B, Greider CW (1995) Functional characterization and developmental regulation of mouse telomerase RNA. Science 269: 1267-1270
12. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91: 25-34
13. Blasco MA, Rizen M, Greider CW, Hanahan D (1996) Differential regulation of telomerase activity and its RNA component during multistage tumorigenesis. Nat Genet 12: 200-204
14. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349-352
15. Broccoli D, Godley LA, Donehower LA, Varmus HE, de Lange T (1996) Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation. Mol Cell Biol 16: 3765-3772
16. Broccoli D, Smogorzewska A, Chong L, de Lange T (1997) Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet 17: 231-235
17. Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR (1997) Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 3: 1271-1274
18. Canela A, Martín-Caballero J, Flores JM, Blasco MA (2004) Constitutive expression of Tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice. Mol Cell Biol 24: 4275-4293
19. Cenci G, Siriaco G, Raffa GD, Kellum R, Gatti M (2003) The Drosophila HOAP protein is required for telomere capping. Nat Cell Biol 1: 82-84
20. Chan SW-L, Blackburn EH (2002) New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene 21: 553-563
21. Chang S, Multan AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36: 877-882
22. Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA (1999) p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97: 527-538
23. Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempst P, de Lange T (1995) A human telomeric protein. Science 270: 1663-1667
24. Collins K (2000) Mammalian telomeres and telomerase. Curr Opin Cell Biol 12: 378-383
25. Collins K, Mitchell JR (2002) Telomerase in the human organism. Oncogene 21: 564-579
26. Dantzer F, Giraud-Panis MJ, Jaco I, Ame JC, Schultz I, Blasco MA, Koering CE, Gilson E, Menissier-de Murcia J, de Murcia G, Schreiber V (2004) Functional interaction between poly(ADP-ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2. Mol Cell Biol 24: 1595-1607
27. De Lange T (2002) Protection of mammalian telomeres. Oncogene 21: 532-540
28. De Lange T (2004) T-loops and the origin of telomeres. Nat Rev Mol Cell Biol 5: 323-329
29. Dunham MA, Neumann AA, Fasching CL, Reddel RR (2000) Telomere maintenance by recombination in human cells. Nat Genet 26: 447-450
30. Dynek JN, Smith S (2004) Resolution of sister telomere association is required for progression through mitosis. Science 304: 97-100
31. Espejel S, Franco S, Rodríguez-Perales S, Bouffler SD, Cigudosa JC, Blasco MA (2002a) Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J 21: 2207-2219
32. Espejel S, Franco S, Sgura A, Gae D, Bailey S, Taccioli G, Blasco MA (2002b) Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. EMBO J 21: 6275-6287
33. Espejel S, Klatt P, Martín-Caballero JM, Flores J, Blasco MA (2004) Shorter telomeres, accelerated aging and increased lymphoma in DNA-PKcs-deficient mice. EMBO Rep 5: 503-509
34. Fanti L, Giovinazzo G, Berloco M, Pimpinelli S (1998) The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol Cell 2: 527-538
35. Ferron S, Mira E, Franco S, Cano-Jaimez M, Bellmunt E, Ramirez C, Fariñas I, Blasco MA (2004) Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 131: 4059-4070
36. Franco S, Segura I, Riese H, Blasco MA (2002) Telomere length is a key molecular determinant of angiogenic potential in vivo: implications for cancer and aging. Cancer Res 62: 552-559
37. García-Cao M, Gonzalo S, Dean D, Blasco MA (2002) Role of the Rb family members in controlling telomere length. Nat Genet 32: 415-419
38. Garcia-Cao M, O'Sullivan R, Peters AH, Jenuwein T, Blasco MA (2004) Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet 36: 94-99
39. Gilley D, Tanaka H, Hande MP, Kurimasa A, Li GC, Oshimura M, Chen DJ (2001) DNA-PKcs is critical for telomere capping. Proc Natl Acad Sci USA 98: 15084-15088
40. González-Suárez E, Flores JM, Blasco MA (2002) Coorperation between p53 mutation and high telomerase transgenic expression in spontaneous cancer development. Mol Cell Biol 22: 7291-7301
41. González-Suárez E, Geserick C, Flores JM, Blasco MA (2005) Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene [E-pub ahead of print: 31 January 2005]
42. González-Suárez E, Samper E, Flores JM, Blasco MA (2000) Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet 26: 114-117
43. González-Suárez E, Samper E, Ramirez A, Flores JM, Martin-Caballero J, Jorcano JL, Blasco MA (2001) Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J 20: 2619-2630
44. Goytisolo FA, Blasco MA (2002) Many ways to telomere dysfunction: in vivo studies using mouse models. Oncogene 21: 584-591
45. Goytisolo FA, Samper E, Edmonson S, Taccioli GE, Blasco MA (2001) The absence of the DNA-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang. Mol Cell Biol 21: 3642-3651
46. Goytisolo FA, Samper E, Martin-Caballero J, Finnon P, Herrera E, Flores JM, Bouffler SD, Blasco MA (2000) Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals. J Exp Med 192: 1625-1636
47. Greenberg RA, Chin L, Femino A, Lee KH, Gottlieb GJ, Singer RH, Greider CW, DePinho RA (1999) Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 97: 515-525
48. Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43: 405-413
49. Greider CW, Blackburn EH (1987) The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51: 887-898
50. Greider CW, Blackburn EH (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337: 331-337
51. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop. Cell 97: 503-514
52. Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345: 458-460
53. Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, Grunstein M (1995) Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell 80: 583-592
54. Hemann MT, Rudolph KL, Strong MA, DePinho RA, Chin L, Greider CW (2001a) Telomere dysfunction triggers developmentally regulated germ cell apoptosis. Mol Biol Cell 12: 2023
55. Hemann MT, Strong MA, Hao LY, Greider CW (2001b) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107: 67-77
56. Henson JD, Neumann AA, Yeager TR, Reddel RR (2002) Alternative lengthening of telomeres in mammalian cells. Oncogene 21: 598-610
57. Herrera E, Martinez AC, Blasco MA (2000) Impaired germinal center reaction in mice with short telomeres. EMBO J 19: 472-481
58. Herrera E, Samper E, Blasco MA (1999b) Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. EMBO J 18: 1172-1181
59. Herrera E, Samper E, Martin-Caballero J, Flores JM, Lee HW, Blasco MA (1999a) Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 18: 2950-2960
60. Hiyama E, Hiyama K (2002) Clinical utility of telomerase in cancer. Oncogene 21: 643-649
61. Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ (2000) Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev 14: 2807-2812
62. Jaco I, Muñoz P, Blasco MA (2004) Role of human Ku86 in telomere length maintenance and telomere capping. Cancer Res 64: 7271-7278
63. Jaco I, Muñoz P, Goytisolo FA, Wesoly J, Bailey S, Taccioli G, Blasco MA (2003) Role of mammalian Rad54 in telomere length maintenance. Mol Cell Biol 23: 5572-5580
64. Jenuwein T (2001) Re-SET-ting heterochromatin by histone methyl-transferases. Trends Cell Biol 11: 266-273
65. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074-1080
66. Kaminker PG, Kim SH, Taylor RD, Zebarjadian Y, Funk WD, Morin GB, Yaswen P, Campisi J (2001) TANK2, a new TRF1-associated PARP, causes rapid induction of cell death upon overexpression. J Biol Chem 276: 35891-35899
67. Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JH, Lange T (2004) The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol 2, E240 (Epub 2004 August 17)
68. Karlseder J, Kachatrian L, Takai H, Mercer K, Ignoran S, Jacks T, de Lange T (2003) Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol Cell Biol 23: 6533-6541
69. Kim SH, Beausejour C, Dávalos AR, Kaminker P, Heo SJ, Campisi J (2004) TIN2 mediates functions of TRF2 at human telomeres. J Biol Chem 279: 43799-43804
70. Kim SH, Kaminker P, Campisi J (1999) TIN2, a new regulator of telomere length in human cells. Nat Genet 23: 405-412
71. Koering CE, Pollice A, Zibella MP, Bauwens S, Puisieux A, Brunori M, Brun C, Martins L, Sabatier L, Pulitzer JF, Wilson E (2002) Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep 3: 1055-1061
72. Lachner M, O'Carrol D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116-120
73. Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD (2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 288: 665-669
74. Latre L, Tusell L, Martín M, Miró R, Egozcue J, Blasco MA, Genescá A (2003) Shortened telomeres join DNA breaks interfering with their correct repair. Exp Cell Res 287: 282-288
75. Lee HW, Blasco MA, Gottlieb GJ, Horner JW, Greider CW, DePinho RA (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392: 569-574
76. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, Nadal-Ginard B, Kajstura J, Anversa P, Blasco MA (2003) Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure. EMBO J 22: 131-139
77. Li B, de Lange T (2003) Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell 14: 5060-5068
78. Li B, Oestreich S, de Lange T (2000) Identification of human Rap1: implications for telomere evolution. Cell 101: 471-483
79. Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6: 673-680
80. Loayza D, De Lange T (2003) POT1 as a terminal transducer of TRF1 telomere length control. Nature 423: 1013-1018
81. Lundblad V (2002) Telomere maintenance without telomerase. Oncogene 21: 522-531
82. Martin-Rivera L, Herrera E, Albar JP, Blasco MA (1998) Expression of mouse telomerase catalytic subunit in embryos and adult tissues. Proc Natl Acad Sci USA 95: 10471-10476
83. Mattson MP, Fu W, Zhang P (2001) Emerging roles for telomerase in regulating cell differentiation and survival: a neuroscientist's perspective. Mech Aging Dev 122: 659-671
84. McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26: 234-282
85. Myung K, Ghosh G, Fattah FJ, Li G, Kim H, Dutia A, Pak E, Smith S, Hendrickson EA (2004) Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. Mol Cell Biol 24: 5050-5059
86. Nikitina T, Woodcock CL (2004) Chromatin loops at the ends of chromosomes. J Cell Biol 166: 161-165
87. Opresko PL, Otterlei M, Graakjaer J, Bruheim P, Dawut L, Kolvraa S, May A, Seidman MM, Bohr VA (2004) The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol Cell 14: 763-774
88. Perrod S, Gasser SM (2003) Long-range silencing and position effects at telomeres and centromeres: parallels and differences. Cell Mol Life Sci 60: 2303-2318
89. Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y, Martens JH, Jenuwein T (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 12: 1577-1589
90. Peters AH, O'Carroll D, Scherthan H, Mechtler K, Sauer S, Schofer C, Weipoltshammer K, Pagani M, Lachner M, Kohlmaier A, Opravil S, Doyle M, Sibilia M, Jenuwein T (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107: 323-337
91. Riha K, Watson JM, Parkey J, Shippen DE (2002) Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J 21: 2819-2826
92. Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96: 701-712
93. Rudolph KL, Millard M, Bosenberg MW, DePinho RA (2001) Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28: 155-159
94. Samper E, Fernández P, Martín-Rivera L, Bernad A, Blasco MA, Aracil M (2002) Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood 99: 2767-2775
95. -/- mice with short telomeres. EMBO Rep 2: 1-8
96. Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA (2000) Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep 1: 244-252
97. Savitsky M, Kravchuk O, Melnikova L, Georgiev P (2002) Heterochromatin protein 1 is involved in control of telomere elongation in Drosophila melanogaster. Mol Cell Biol 22: 3204-3218
98. Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T (2004) A silencing pathway to induce H3-K9 and H4-K20 tri-methylation at constitutive heterochromatin. Genes Dev 8: 1251-1262
99. Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE (1999) Analysis of telomere lengths in cloned sheep. Nature 399: 316-317
100. Smith GC, Jackson SP (1999) The DNA-dependent protein kinase. Genes Dev 13: 916-934
101. Smith LL, Coller HA, Roberts JM (2003) Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nat Cell Biol 5: 474-479
102. Smith S, Giriat I, Schmitt A, de Lange T (1998) Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282: 1484-1487
103. Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T (2000) Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 20: 1659-1668
104. Song K, Jung D, Jung Y, Lee SG, Lee I (2000) Interaction of human Ku70 with TRF2. FEBS Lett 481: 81-85
105. Tarsounas M, Muñoz P, Claas A, Smiraldo PH, Pittman DL, Blasco MA, West SC (2004) Telomere maintenance requires the RAD51D recombination/repair protein. Cell 117: 337-347
106. Tommerup H, Dousmanis A, de Lange T (1994) Unusual chromatin in human telomeres. Mol Cell Biol 14: 5777-5785
107. van Steensel B, Smogorzewska A, de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92: 401-413
108. Wang RC, Smogorzewska A, de Lange T (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119: 355-368
109. Watson JD (1972) Origin of concatemeric T7DNA. Nat New Biol 239: 197-201
110. 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) Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet 26: 85-88
111. Wong KK, Maser RS, Bachoo RM, Menon J, Carrasco DR, Gu Y, Alt FW, DePinho RA (2003) Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 421: 643-648
112. Ye JZ, de Lange T (2004a) TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Nat Genet 36: 618-623
113. Ye JZ, Donigian JR, Van Overbeek M, Loayza D, Luo Y, Krutchinsky AN, Chait BT, De Lange T (2004b) TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem 279: 47264-47271
114. Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004c) POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18: 1649-1654
115. Zhu XD, Kuster B, Mann M, Petrini JH, Lange T (2000) Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet 25: 347-352
116. Zhu XD, Niedernhofer L, Kuster B, Mann M, Hoeijmakers JH, de Lange T (2003) ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 12: 1489-1498
117. Zijlmans JM, Martens UM, Poon SS, Raap AK, Tanke HJ, Ward RK, Lansdorp PM (1997) Telomeres in the mouse have large interchromosomal variations in the number of T2AG3 repeats. Proc Natl Acad Sci USA 94: 7423-7428