A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice

Genes and Development

Volumn 28, Issue 2, 2014, Pages 153-166

  Frescas, David ^a   de Lange, Titia ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Dyskeratosis congenita; Shelterin; Telomerase; Telomere; Telomeropathy; TIN2

Indexed keywords

PROTEIN; TELOMERASE; TIN2 PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; CELL PROLIFERATION; CONTROLLED STUDY; DYSKERATOSIS CONGENITA; FERTILITY; FIBROBLAST; GENE MUTATION; GENE TARGETING; MOUSE; NONHUMAN; PANCYTOPENIA; PRIORITY JOURNAL; REVIEW; TELOMERE HOMEOSTASIS; TELOMERE SHORTENING;

DYSKERATOSIS CONGENITA; SHELTERIN; TELOMERASE; TELOMERE; TELOMEROPATHY; TIN2;

ANIMALS; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; DYSKERATOSIS CONGENITA; FERTILITY; GENE KNOCK-IN TECHNIQUES; HELA CELLS; HUMANS; MICE; MUTATION; PANCYTOPENIA; SIGNAL TRANSDUCTION; TELOMERASE; TELOMERE; TELOMERE SHORTENING; TELOMERE-BINDING PROTEINS;

EID: 84892723396     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.233395.113     Document Type: Review

References (65)

1. Abreu E, Aritonovska E, Reichenbach P, Cristofari G, Culp B, Terns RM, Lingner J, Terns MP. 2010. TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. Mol Cell Biol 30: 2971-2982.
2. Alter BP, Baerlocher GM, Savage SA, Chanock SJ, Weksler BB, Willner JP, Peters JA, Giri N, Lansdorp PM. 2007. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 110: 1439-1447.
3. Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O'Sullivan J, et al. 2012. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet 44: 338-342.
4. Armanios M. 2009. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet 10: 45-61.
5. Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, et al. 2005. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci 102: 15960-15964.
6. Aubert G, Lansdorp PM. 2008. Telomeres and aging. Physiol Rev 88: 557-579.
7. Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O'Reilly R, Manschreck C, et al. 2013a. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of hoyeraal hreidarsson syndrome. PLoS Genet 9: e1003695.
8. Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA. 2013b. Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in dyskeratosis congenita. Hum Genet 132: 473-480.
9. 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.
10. Calado RT, Young NS. 2009. Telomere diseases. N Engl J Med 361: 2353-2365.
11. Canela A, Vera E, Klatt P, Blasco MA. 2007. High-throughput telomere length quantification by FISH and its application to human population studies. Proc Natl Acad Sci 104: 5300-5305.
12. Canudas S, Houghtaling BR, Bhanot M, Sasa G, Savage SA, Bertuch AA, Smith S. 2011. A role for heterochromatin protein 1γ at human telomeres. Genes Dev 25: 1807-1819.
13. Celli GB, de Lange T. 2005. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7: 712-718.
14. Celli GB, Lazzerini Denchi E, de Lange T. 2006. Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol 8: 885-890.
15. Chen Y, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, Lei M. 2008. A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science 319: 1092-1096.
16. Denchi EL, de Lange T. 2007. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448: 1068-1071.
17. Deng Z, Glousker G, Molczan A, Fox AJ, Lamm N, Dheekollu J, Weizman OE, Schertzer M, Wang Z, Vladimirova O, et al. 2013. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome. Proc Natl Acad Sci 110: E3408-E3416.
18. Dokal I, Vulliamy T. 2005. Telomerase deficiency and human disease. In Telomeres. (ed. de Lange T, et al.), pp. 139-162. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
19. He H, Wang Y, Guo X, Ramchandani S, Ma J, Shen MF, Garcia DA, Deng Y, Multani AS, You MJ, et al. 2009. Pot1b deletion and telomerase haploinsufficiency in mice initiate an ATRdependent DNA damage response and elicit phenotypes resembling dyskeratosis congenita. Mol Cell Biol 29: 229-240.
20. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I. 1998. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 19: 32-38.
21. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. 2004. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14: 501-513.
22. Hockemeyer D, Palm W, Wang RC, Couto SS, de Lange T. 2008. Engineered telomere degradation models dyskeratosis congenita. Genes Dev 22: 1773-1785.
23. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA. 2001. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15: 3243-3248.
24. Kim SH, Kaminker P, Campisi J. 1999. TIN2, a new regulator of telomere length in human cells. Nat Genet 23: 405-412.
25. Kim SH, Beausejour C, Davalos AR, Kaminker P, Heo SJ, Campisi J. 2004. TIN2 mediates functions of TRF2 at human telomeres. J Biol Chem 279: 43799-43804.
26. Le Guen T, Jullien L, Touzot F, Schertzer M, Gaillard L, Perderiset M, Carpentier W, Nitschke P, Picard C, Couillault G, et al. 2013. Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability. Hum Mol Genet 22: 3239-3249.
27. Liu D, O'Connor MS, Qin J, Songyang Z. 2004a. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem 279: 51338-51342.
28. Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z. 2004b. PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6: 673-680.
29. Loayza D, de Lange T. 2003. POT1 as a terminal transducer of TRF1 telomere length control. Nature 424: 1013-1018.
30. Marrone A, Stevens D, Vulliamy T, Dokal I, Mason PJ. 2004. Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency. Blood 104: 3936-3942.
31. Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T, Dokal I. 2007. Telomerase reversetranscriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood 110: 4198-4205.
32. Mason PJ, Wilson DB, Bessler M. 2005. Dyskeratosis congenita-a disease of dysfunctional telomere maintenance. Curr Mol Med 5: 159-170.
33. Mitchell JR, Wood E, Collins K. 1999. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402: 551-555.
34. Nandakumar J, Bell CF, Weidenfeld I, Zaug AJ, Leinwand LA, Cech TR. 2012. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature 492: 285-289.
35. Nelson ND, Bertuch AA. 2012. Dyskeratosis congenita as a disorder of telomere maintenance. Mutat Res 730: 43-51.
36. Neumann AA, Watson CM, Noble JR, Pickett HA, Tam PP, Reddel RR. 2013. Alternative lengthening of telomeres in normal mammalian somatic cells. Genes Dev 27: 18-23.
37. O'Connor MS, Safari A, Xin H, Liu D, Songyang Z. 2006. A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci 103: 11874-11879.
38. Palm W, de Lange T. 2008. How shelterin protects mammalian telomeres. Annu Rev Genet 42: 301-334.
39. Poon SS, Lansdorp PM. 2001. Quantitative fluorescence in situ hybridization (Q-FISH). Curr Protoc Cell Biol 12: 18.4.1-18.4.21.
40. 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.
41. Sarper N, Zengin E, Kilic SC. 2010. A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex. Pediatr Blood Cancer 55: 1185-1186.
42. Savage SA, Bertuch AA. 2010. The genetics and clinical manifestations of telomere biology disorders. Genet Med 12: 753-764.
43. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. 2008. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet 82: 501-509.
44. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T. 2009. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138: 90-103.
45. Takai KK, Hooper S, Blackwood S, Gandhi R, de Lange T. 2010. In vivo stoichiometry of shelterin components. J Biol Chem 285: 1457-1467.
46. Takai KK, Kibe T, Donigian JR, Frescas D, de Lange T. 2011. Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell 44: 647-659.
47. Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, Oyarzabal J, Pastor J, Bischoff JR, Fernandez-Capetillo O. 2011. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol 18: 721-727.
48. Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, de Villartay JP, Revy P. 2010. Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome. Proc Natl Acad Sci 107: 10097-10102.
49. Trahan C, Martel C, Dragon F. 2010. Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs. Hum Mol Genet 19: 825-836.
50. Tsangaris E, Adams SL, Yoon G, Chitayat D, Lansdorp P, Dokal I, Dror Y. 2008. Ataxia and pancytopenia caused by a mutation in TINF2. Hum Genet 124: 507-513.
51. Vannier JB, Pavicic-Kaltenbrunner V, Petalcorin MI, Ding H, Boulton SJ. 2012. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell 149: 795-806.
52. Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I. 2001. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413: 432-435.
53. Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I. 2004. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 36: 447-449.
54. Vulliamy T, Beswick R, Kirwan M, Marrone A, Digweed M, Walne A, Dokal I. 2008. Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci 105: 8073-8078.
55. Walne AJ, Vulliamy T, Marrone A, Beswick R, Kirwan M, Masunari Y, Al-Qurashi FH, Aljurf M, Dokal I. 2007. Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomeraseassociated protein NOP10. Hum Mol Genet 16: 1619-1629.
56. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. 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: 3594-3600.
57. Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I. 2013. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am J Hum Genet 92: 448-453.
58. Wang RC, Smogorzewska A, de Lange T. 2004. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119: 355-368.
59. Wu P, van Overbeek M, Rooney S, de Lange T. 2010. Apollo contributes to G overhang maintenance and protects leading-end telomeres. Mol Cell 39: 1-12.
60. Xin ZT, Ly H. 2012. Characterization of interactions between naturally mutated forms of the TIN2 protein and its known protein partners of the shelterin complex. Clin Genet 81: 301-302.
61. Yang D, He Q, Kim H, Ma W, Songyang Z. 2011. TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase. J Biol Chem 286: 23022-23030.
62. Ye JZ, de Lange T. 2004. TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Nat Genet 36: 618-623.
63. Ye JZ, Donigian JR, Van Overbeek M, Loayza D, Luo Y, Krutchinsky AN, Chait BT, de Lange T. 2004. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem 279: 47264-47271.
64. Zhong F, Savage SA, Shkreli M, Giri N, Jessop L, Myers T, Chen R, Alter BP, Artandi SE. 2011. Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita. Genes Dev 25: 11-16.
65. Zhong FL, Batista LF, Freund A, Pech MF, Venteicher AS, Artandi SE. 2012. TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell 150: 481-494.