Alternative lengthening of telomeres pathway: Recombination-mediated telomere maintenance mechanism in human cells

Journal of Biochemistry

Volumn 149, Issue 1, 2011, Pages 5-14

  Nabetani, Akira ^a   Ishikawa, Fuyuki ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

alternative lengthening of telomeres (ALT); extrachromosomal telomeric repeat (ECTR); PML body; recombination; telomere

Indexed keywords

DNA; DNA BINDING PROTEIN; DNA METHYLTRANSFERASE; HELICASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOINOSITIDE 3 KINASE RELATED KINASE; PROTEIN MRN; PROTEIN SHELTERIN; RECQ HELICASE; TELOMERASE; TELOMERIC REPEAT BINDING FACTOR 2; UNCLASSIFIED DRUG; XRCC3 PROTEIN;

CELL DIVISION; CELL PROLIFERATION; CHROMATID; CHROMATIN; DNA METABOLISM; DNA RECOMBINATION; DNA STRUCTURE; DNA SYNTHESIS; ENZYME LOCALIZATION; GENE DELETION; GENE MUTATION; HOMOLOGOUS RECOMBINATION; HUMAN; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; SOMATIC CELL; SUMOYLATION; TELOMERE;

ANIMALS; CELL CYCLE PROTEINS; DNA; DNA HELICASES; DNA REPAIR ENZYMES; DNA, CRUCIFORM; DNA-BINDING PROTEINS; HUMANS; NUCLEAR PROTEINS; RECOMBINATION, GENETIC; TELOMERASE; TELOMERE; TELOMERE-BINDING PROTEINS; TELOMERIC REPEAT BINDING PROTEIN 2;

EID: 78650662899     PISSN: 0021924X     EISSN: 17562651     Source Type: Journal    
DOI: 10.1093/jb/mvq119     Document Type: Review

References (79)

1. Wellinger, R.J., Wolf, A.J., and Zakian, V.A. (1993) Saccharomyces telomeres acquire single-strand TG1-3 tails late in S phase. Cell 72, 51-60
2. Griffith, J.D., Comeau, L., Rosenfield, S., Stansel, R.M., Bianchi, A., Moss, H., and de Lange, T. (1999) Mammalian telomeres end in a large duplex loop. Cell 97, 503-514
3. de Lange, T. (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110
4. Miyoshi, T., Kanoh, J., Saito, M., and Ishikawa, F. (2008) Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Science 320, 1341-1344
5. Olovnikov, A.M. (1973) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol. 41, 181-190
6. Watson, J.D. (1972) Origin of concatemeric T7 DNA. Nat. New Biol. 239, 197-201
7. Harley, C.B., Futcher, A.B., and Greider, C.W. (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460
8. Hayflick, L. and Moorhead, P.S. (1961) The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585-621
9. Greider, C.W. and Blackburn, E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413
10. Bryan, T.M., Englezou, A., Dalla-Pozza, L., Dunham, M.A., and Reddel, R.R. (1997) Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 3, 1271-1274
11. Naito, T., Matsuura, A., and Ishikawa, F. (1998) Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nat. Genet. 20, 203-206
12. Nakamura, T.M., Cooper, J.P., and Cech, T.R. (1998) Two modes of survival of fission yeast without telomer-ase. Science 282, 493-496
13. Blasco, M.A., Lee, H.W., Hande, M.P., Samper, E., Lansdorp, P.M., DePinho, R.A., and Greider, C.W. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25-34
14. Lundblad, V. and Szostak, J.W. (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633-643
15. Yuan, X., Ishibashi, S., Hatakeyama, S., Saito, M., Nakayama, J., Nikaido, R., Haruyama, T., Watanabe, Y., Iwata, H., Iida, M., Sugimura, H., Yamada, N., and Ishikawa, F. (1999) Presence of telo-meric G-strand tails in the telomerase catalytic subunit TERT knockout mice. Genes Cells 4, 563-572
16. Bryan, T.M., Englezou, A., Gupta, J., Bacchetti, S., and Reddel, R.R. (1995) Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 14, 4240-4248
17. Perrem, K., Colgin, L.M., Neumann, A.A., Yeager, T.R., and Reddel, R.R. (2001) Coexistence of alternative lengthening of telomeres and telomerase in hTERT-transfected GM847 cells. Mol. Cell Biol. 21, 3862-3875
18. Murnane, J.P., Sabatier, L., Marder, B.A., and Morgan, W.F. (1994) Telomere dynamics in an immortal human cell line. EMBO J. 13, 4953-4962
19. Dunham, M.A., Neumann, A.A., Fasching, C.L., and Reddel, R.R. (2000) Telomere maintenance by recombination in human cells. Nat. Genet. 26, 447-450
20. Jeyapalan, J.N., Varley, H., Foxon, J.L., Pollock, R.E., Jeffreys, A.J., Henson, J.D., Reddel, R.R., and Royle, N.J. (2005) Activation of the ALT pathway for telomere maintenance can affect other sequences in the human genome. Hum. Mol. Genet. 14, 1785-1794
21. Tsutsui, T., Kumakura, S., Tamura, Y., Tsutsui, T.W., Sekiguchi, M., Higuchi, T., and Barrett, J.C. (2003) Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities. Carcinogenesis 24, 953-965
22. Bechter, O.E., Zou, Y., Shay, J.W., and Wright, W.E. (2003) Homologous recombination in human telomer- ase-positive and ALT cells occurs with the same frequency. EMBO Rep. 4, 1138-1143
23. Bailey, S.M., Brenneman, M.A., and Goodwin, E.H. (2004) Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res. 32, 3743-3751
24. Bechter, O.E., Shay, J.W., and Wright, W.E. (2004) The frequency of homologous recombination in human ALT cells. Cell Cycle 3, 547-549
25. Londono-Vallejo, J.A., Der-Sarkissian, H., Cazes, L., Bacchetti, S., and Reddel, R.R. (2004) Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res. 64, 2324-2327
26. Tokutake, Y., Matsumoto, T., Watanabe, T., Maeda, S., Tahara, H., Sakamoto, S., Niida, H., Sugimoto, M., Ide, T., and Furuichi, Y. (1998) Extra-chromosomal telomere repeat DNA in telomerase-negative immortalized cell lines. Biochem. Biophys. Res. Commun. 247, 765-772
27. Ogino, H., Nakabayashi, K., Suzuki, M., Takahashi, E., Fujii, M., Suzuki, T., and Ayusawa, D. (1998) Release of telomeric DNA from chromosomes in immortal human cells lacking telomerase activity. Biochem. Biophys. Res. Commun. 248, 223-227
28. Cesare, A.J. and Griffith, J.D. (2004) Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol. Cell Biol. 24, 9948-9957
29. Wang, R.C., Smogorzewska, A., and de Lange, T. (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355-368
30. Pickett, H.A., Cesare, A.J., Johnston, R.L., Neumann, A.A., and Reddel, R.R. (2009) Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO J. 28, 799-809
31. Nabetani, A. and Ishikawa, F. (2009) Unusual telomeric DNAs in human telomerase-negative immortalized cells. Mol. Cell Biol. 29, 703-713
32. Henson, J.D., Cao, Y., Huschtscha, L.I., Chang, A.C., Au, A.Y., Pickett, H.A., and Reddel, R.R. (2009) DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity. Nat. Biotechnol. 27, 1181-1185
33. Nosek, J., Rycovska, A., Makhov, A.M., Griffith, J.D., and Tomaska, L. (2005) Amplification of telomeric arrays via rolling-circle mechanism. J. Biol. Chem. 280, 10840-10845
34. Yeager, T.R., Neumann, A.A., Englezou, A., Huschtscha, L.I., Noble, J.R., and Reddel, R.R. (1999) Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 59, 4175-4179
35. Grobelny, J.V., Godwin, A.K., and Broccoli, D. (2000) ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle. J. Cell Sci. 113(Pt 24), 4577-4585
36. Nabetani, A., Yokoyama, O., and Ishikawa, F. (2004) Localization of hRad9, hHus1, hRad1, and hRad17 and caffeine-sensitive DNA replication at the alternative lengthening of telomeres-associated promyelocytic leukemia body. J. Biol. Chem. 279, 25849-25857
37. Cesare, A.J., Kaul, Z., Cohen, S.B., Napier, C.E., Pickett, H.A., Neumann, A.A., and Reddel, R.R. (2009) Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nat. Struct. Mol. Biol. 16, 1244-1251
38. Draskovic, I., Arnoult, N, Steiner, V., Bacchetti, S., Lomonte, P., and Londono-Vallejo, A. (2009) Probing PML body function in ALT cells reveals spatiotemporal requirements for telomere recombination. Proc. Natl Acad. Sci. USA 106, 15726-15731
39. Fasching, C.L., Neumann, A.A., Muntoni, A., Yeager, T.R., and Reddel, R.R. (2007) DNA damage induces alternative lengthening of telomeres (ALT) associated promyelocytic leukemia bodies that preferentially associate with linear telomeric DNA. Cancer Res. 67, 7072-7077
40. Jiang, W.Q., Zhong, Z.H., Henson, J.D., Neumann, A.A., Chang, A.C., and Reddel, R.R. (2005) Suppression of alternative lengthening of telomeres by Sp100-mediated sequestration of the MRE11/RAD50/ NBS1 complex. Mol. Cell Biol. 25, 2708-2721
41. Potts, P.R. and Yu, H. (2007) The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat. Struct. Mol. Biol. 14, 581-590
42. Zhong, Z.H., Jiang, W.Q., Cesare, A.J., Neumann, A.A., Wadhwa, R., and Reddel, R.R. (2007) Disruption of telomere maintenance by depletion of the MRE11/ RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J. Biol. Chem. 282, 29314-29322
43. Jiang, W.Q., Zhong, Z.H., Henson, J.D., and Reddel, R.R. (2007) Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene 26, 4635-4647
44. Compton, S.A., Choi, J.H., Cesare, A.J., Ozgur, S., and Griffith, J.D. (2007) Xrcc3 and Nbs1 are required for the production of extrachromosomal telomeric circles in human alternative lengthening of telomere cells. Cancer Res. 67, 1513-1519
45. van Steensel, B., Smogorzewska, A., and de Lange, T. (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401-413
46. Stagno D'Alcontres, M., Mendez-Bermudez, A., Foxon, J.L., Royle, N.J., and Salomoni, P. (2007) Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA. J. Cell Biol 179, 855-867
47. Bhattacharyya, S., Keirsey, J., Russell, B., Kavecansky, J., Lillard-Wetherell, K., Tahmaseb, K., Turchi, J.J., and Groden, J. (2009) Telomerase-associated protein 1, HSP90, and topoisomerase IIalpha associate directly with the BLM helicase in immortalized cells using ALT and modulate its helicase activity using telomeric DNA substrates. J. Biol. Chem. 284, 14966-14977
48. Temime-Smaali, N, Guittat, L., Wenner, T., Bayart, E., Douarre, C, Gomez, D., Giraud-Panis, M.J., Londono-Vallejo, A., Gilson, E., Amor-Gueret, M., and Riou, J.F. (2008) Topoisomerase IIIalpha is required for normal proliferation and telomere stability in alternative lengthening of telomeres. EMBO J. 27, 1513-1524
49. Wu, L. and Hickson, I.D. (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870-874
50. Fasching, C.L., Bower, K., and Reddel, R.R. (2005) Telomerase-independent telomere length maintenance in the absence of alternative lengthening of telomeres-associated promyelocytic leukemia bodies. Cancer Res. 65, 2722-2729
51. Marciniak, R.A., Cavazos, D., Montellano, R., Chen, Q., Guarente, L., and Johnson, F.B. (2005) A novel telomere structure in a human alternative lengthening of telomeres cell line. Cancer Res. 65, 2730-2737
52. Laud, P.R., Multani, A.S., Bailey, S.M., Wu, L., Ma, J., Kingsley, C, Lebel, M., Pathak, S., DePinho, R.A., and Chang, S. (2005) Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 19, 2560-2570
53. Zeng, S., Xiang, T., Pandita, T.K., Gonzalez-Suarez, I., Gonzalo, S., Harris, C.C., and Yang, Q. (2009) Telomere recombination requires the MUS81 endonuclease. Nat. Cell Biol. 11, 616-623
54. Tarsounas, M., Munoz, P., Claas, A., Smiraldo, P.G., Pittman, D.L., Blasco, M.A., and West, S.C. (2004) Telomere maintenance requires the RAD51D recombination/repair protein. Cell 117, 337-347
55. Saharia, A. and Stewart, S.A. (2009) FEN1 contributes to telomere stability in ALT-positive tumor cells. Oncogene 28, 1162-1167
56. Grudic, A., Jul-Larsen, A., Haring, S.J., Wold, M.S., Lønning, P.E., Bjerkvig, R., and Bøe, S.O. (2007) Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres. Nucleic Acids Res. 35, 7267-7278
57. Fan, Q., Zhang, F., Barrett, B., Ren, K., and Andreassen, P.R. (2009) A role for monoubiquitinated FANCD2 at telomeres in ALT cells. Nucleic Acids Res. 37, 1740-1754
58. Jiang, W.Q., Zhong, Z.H., Nguyen, A., Henson, J.D., Toouli, CD., Braithwaite, A.W., and Reddel, R.R. (2009) Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins. J. Cell Biol 185, 797-810
59. De'jardin, J. and Kingston, R.E. (2009) Purification of proteins associated with specific genomic Loci. Cell 136, 175-186
60. Perrem, K., Bryan, T.M., Englezou, A., Hackl, T., Moy, E.L., and Reddel, R.R. (1999) Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. Oncogene 18, 3383-3390
61. Lundblad, V. and Blackburn, E.H. (1993) An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73, 347-360
62. Teng, S.C. and Zakian, V.A. (1999) Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol. Cell Biol. 19, 8083-8093
63. Lin, C.Y., Chang, H.H., Wu, K.J., Tseng, S.F., Lin, C.C., Lin, C.P., and Teng, S.C. (2005) Extrachro-mosomal telomeric circles contribute to Rad52-, Rad50-, and polymerase delta-mediated telomere-telomere recombination in Saccharomyces cerevisiae. Eukaryot. Cell 4, 327-336
64. Natarajan, S., Groff-Vindman, C, and McEachern, M.J. (2003) Factors influencing the recombinational expansion and spread of telomeric tandem arrays in Kluyveromyces lactis. Eukaryot Cell 2, 1115-1127
65. Natarajan, S. and McEachern, M.J. (2002) Recombinational telomere elongation promoted by DNA circles. Mol. Cell Biol. 22, 4512-4521
66. Niida, H., Shinkai, Y., Hande, M.P., Matsumoto, T., Takehara, S., Tachibana, M., Oshimura, M., Lansdorp, P.M., and Furuichi, Y. (2000) Telomere maintenance in telomerase-deficient mouse embryonic stem cells: characterization of an amplified telomeric DNA. Mol. Cell Biol. 20, 4115-4127
67. Chang, S., Khoo, CM., Naylor, M.L., Maser, R.S., and DePinho, R.A. (2003) Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Genes Dev. 17, 88-100
68. Gonzalo, S., Jaco, I., Fraga, M.F., Chen, T., Li, E., Esteller, M., and Blasco, M.A. (2006) DNA methyltrans-ferases control telomere length and telomere recombination in mammalian cells. Nat. Cell Biol. 8, 416-424
69. Tilman, G., Loriot, A., Van Beneden, A., Arnoult, N, Londono-Vallejo, J.A., De Smet, C, and Decottignies, A. (2009) Subtelomeric DNA hypomethy-lation is not required for telomeric sister chromatid exchanges in ALT cells. Oncogene 28, 1682-1693
70. Yankiwski, V., Marciniak, R.A., Guarente, L., and Neff, N.F. (2000) Nuclear structure in normal and Bloom syndrome cells. Proc. Natl Acad. Sci. USA 97, 5214-5219
71. Wu, G., Jiang, X., Lee, W.H., and Chen, P.L. (2003) Assembly of functional ALT-associated promyelocytic leukemia bodies requires Nijmegen Breakage Syndrome 1. Cancer Res. 63, 2589-2595
72. Zhu, X.D., Niedernhofer, L., Kuster, B., Mann, M., Hoeijmakers, J.H., and 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
73. Moran-Jones, K., Wayman, L., Kennedy, D.D., Reddel, R.R., Sara, S., Snee, M.J., and Smith, R. (2005) hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere. Nucleic Acids Res. 33, 486-496
74. Zhu, X.D., Kuster, B., Mann, M., Petrini, J.H., and de Lange, T. (2000) Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat. Genet. 25, 347-352 (Pubitemid 30437327)
75. Dantzer, F., Giraud-Panis, M.J., Jaco, I., Ame, J.C., Schultz, I., Blasco, M., Koering, C.E., Gilson, E., Menissier-de Murcia, J., de Murcia, G., and 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
76. Silverman, J., Takai, H., Buonomo, S.B., Eisenhaber, F., and de Lange, T. (2004) Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Genes Dev. 18, 2108-2119
77. Miyake, Y., Nakamura, M., Nabetani, A., Shimamura, S., Tamura, M., Yonehara, S., Saito, M., and Ishikawa, F. (2009) RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol. Cell 36, 193-206
78. Johnson, F.B., Marciniak, R.A., McVey, M., Stewart, S.A., Hahn, W.C., and Guarente, L. (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. EMBO J. 20, 905-913
79. Opresko, P.L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, L., Kølvraa, S., May, A., Seidman, M.M., and Bohr, V.A. (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