Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis

EMBO Journal

Volumn 26, Issue 22, 2007, Pages 4709-4719

  Guo, Xiaolan ^a,b   Deng, Yibin ^a   Lin, Yahong ^a   Cosme Blanco, Wilfredo ^a   Chan, Suzanne ^a   He, Hua ^a   Yuan, Guohua ^b   Brown, Eric J ^c   Chang, Sandy ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b AFFILIATED HOSPITAL OF NORTH SICHUAN MEDICAL COLLEGE   (China)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

ATM ATR; Chromosomal instability; DNA damage; Telomere; Tumorigenesis

Indexed keywords

ATM PROTEIN; ATR PROTEIN; CELL PROTEIN; DNA; PROTEIN P53; PROTEIN POT1A; PROTEIN POT1B; PROTEIN TPP1; REGULATOR PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CARCINOGENESIS; CELL PROTECTION; CELL TRANSFORMATION; CHROMOSOMAL INSTABILITY; CONTROLLED STUDY; DNA DAMAGE; HUMAN; HUMAN CELL; IN VIVO STUDY; MOLECULAR BIOLOGY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; TELOMERE;

ANIMALS; CELL CYCLE PROTEINS; CELLS, CULTURED; DNA DAMAGE; DNA-BINDING PROTEINS; EMBRYO, MAMMALIAN; ENDOPEPTIDASES; FIBROBLASTS; MICE; NEOPLASMS; PROTEIN-SERINE-THREONINE KINASES; RNA, MESSENGER; TELOMERE; TELOMERIC REPEAT BINDING PROTEIN 2; TUMOR SUPPRESSOR PROTEINS;

EID: 36248952723     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/sj.emboj.7601893     Document Type: Article

References (56)

1. Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3: 421-429
2. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J (2005) DNA damage response as a candidate anticancer barrier in early human tumorigenesis. Nature 434: 864-870
3. Bassing CH, Suh H, Ferguson DO, Chua KF, Manis J, Eckersdorff M, Gleason M, Bronson R, Lee C, Alt FW (2003) Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114: 359-370
4. Brown EJ, Baltimore D (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17: 615-628
5. Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296: 550-553
6. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276: 42462-42467
7. Callen E, Jankovic M, Difilippantonio S, Daniel JA, Chen HT, Celeste A, Pellegrini M, McBride K, Wangsa D, Bredemeyer AL, Sleckman BP, Ried T, Nussenzweig M, Nussenzweig A (2007) ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell 130: 63-75
8. Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA, Eckhaus M, Ried T, Bonner WM, Nussenzweig A (2003) H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114: 371-383
9. 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
10. Cosme-Blanco W, Shen MF, Lazar AJ, Pathak S, Lozano G, Multani AS, Chang S (2007) Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 8: 497-503
11. d'Adda di Fagagna FD, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426: 194-198
12. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19: 2100-2110
13. de Lange T (2004) T-loops and the origin of telomeres. Nat Rev Mol Cell Biol 5: 323-329
14. Denchi EL, de Lange T (2007) Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448: 1068-10671
15. Deng Y, Ren X, Yang L, Lin Y, Wu X (2003) A JNK-dependent pathway is required for TNFalpha-induced apoptosis. Cell 115: 61-70
16. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre' M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, d'Adda di Fagagna F (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyperreplication. Nature 444: 638-642
17. Feldser DM, Greider CW (2007) Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell 11: 461-469
18. Francia S, Weiss RS, Hande MP, Freire R, d'Adda di Fagagna F (2006) Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage-checkpoint complex. Curr Biol 16: 1551-1558
19. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio Jr RA, Kastrinakis NG, Levy B, Kletsas D, Yoneta A, Herlyn M, Kittas C, Halazonetis TD (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434: 907-913
20. 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
21. He H, Multani AS, Cosme-Blanco W, Tahara H, Ma J, Pathak S, Deng Y, Chang S (2006) POT1b protects telomeres from end-to-end chromosomal fusions and aberrant homologous recombination. EMBO J 25: 5180-5190
22. 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
23. Hockemeyer D, Daniels JP, Takai H, de Lange T (2006) Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell 126: 63-77
24. Hockemeyer D, Palm W, Else T, Daniels JP, Takai KK, Ye JZ, Keegan CE, de Lange T, Hammer GD (2007) Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol 14: 754-761
25. Houghtaling BR, Cuttonaro L, Chang W, Smith S (2004) A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol 14: 1621-1631
26. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T (1999) p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283: 1321-1325
27. Kelleher C, Kurth I, Lingner J (2005) Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro. Mol Cell Biol 25: 808-818
28. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27: 247-254
29. Kim S, 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
30. Lei M, Zaug AJ, Podell ER, Cech TR (2005) Switching human telomerase on and off with hPOT1 protein in vitro. J Biol Chem 280: 20449-20456
31. Liu D, O'Connor MS, Qin J, Songyang Z (2004b) Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem 279: 51338-51342
32. Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004a) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6: 673-680
33. MacDougall CA, Byun TS, Van C, Yee MC, Cimprich KA (2007) The structural determinants of checkpoint activation. Genes Dev 21: 898-903
34. Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A, O'Neil J, Gutierrez A, Ivanova E, Perna I, Lin E, Mani V, Jiang S, McNamara K, Zaghlul S, Edkins S, Stevens C, Brennan C, Martin ES, Wiedemeyer R, et al (2007) Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447: 966-971
35. Maser RS, DePinho RA (2002) Connecting chromosomes, crisis, and cancer. Science 297: 565-569
36. Nuciforo PG, Luise C, Capra M, Pelosi G, di Fagagna FD (2007) Complex engagement of DNA-damage response pathways in human cancer and in lung tumor progression. Carcinogenesis, May 22; e-pub ahead of print
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 USA 103: 11874-11879
38. O'Hagan RC, Chang S, Maser RS, Mohan R, Artandi SE, Chin L, DePinho RA (2002) Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell 2: 149-155
39. Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 25: 741-747
40. Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM (1998) Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 275: 9390-9395
41. Shiloh Y (2003) ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3: 155-168
42. Takai H, Smogorzewska A, de Lange T (2003) DNA damage foci at dysfunctional telomeres. Curr Bio 13: 1549-1556
43. Theobald DL, Cervantes RB, Lundblad V, Wuttke DS (2003) Homology among telomeric end-protection proteins. Structure 11: 1049-1050
44. Verdun RE, Crabbe L, Haggblom C, Karlseder J (2005) Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell 20: 551-561
45. Verdun RE, Karlseder J (2006) The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127: 709-720
46. Verdun RE, Karlseder J (2007) Replication and protection of telomeres. Nature 447: 924-931
47. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M (2007) The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature 445: 506-510
48. Wong KK, Chang S, Depinho RA (2006) Modeling cancer and aging in the telomerase-deficient mouse. In Telomeres, de Lange T, Lundblad V, Blackburn E (eds), pp 109-138. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
49. Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM, Deng Y, Behringer RR, Chang S (2006) Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126: 49-62
50. Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, O'Connor MS, Songyang Z (2007) TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature 445: 559-562
51. Yang Q, Zheng YL, Harris CC (2005) POT1 and TRF2 cooperate to maintain telomeric integrity. Mol Cell Biol 25: 1070-1080
52. 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
53. Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004a) POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18: 1649-1654
54. Zhou BB, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408: 433-439
55. Zou L (2007) Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes Dev 21: 879-885
56. Zou L, Elledge SJ (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548