Werner syndrome, telomeres, and stress signaling: Implications for future therapies?

Telomeres and Telomerase in Ageing, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Ageing

Volumn , Issue , 2008, Pages 285-308

  Davis, Terence ^a   Kipling, David ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84900966261     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-540-73709-4_14     Document Type: Chapter

References (161)

1. Adelfalk C, Scherthan H, Hirsch-Kauffmann M, Schweiger M (2005) Nuclear deformation characterises Werner syndrome cells. Cell Biol Int 29:1032-37
2. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai E V, Futcher AB, Greider CW, Harley CB (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89:10114-18
3. Anderson DR, Hegde S, Reinhard E, Gomez L, Vernier WF, Lee L, Liu S, Sambandam A, Snider PA, Masih L (2005) Aminocyanopyridine inhibitors of mitogen activated protein kinaseactivated protein kinase 2 (MK-2). Bioorg Med Chem Lett 15:1587-90
4. Bai Y, Murnane JP (2003) Telomere instability in a human tumor cell line expressing a dominantnegative WRN protein. Hum Genet 113:337-47
5. Baird DM, Davis T, Rowson J, Jones CJ, Kipling D (2004) Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells. Hum Mol Genet 13:1515-24
6. Beddy DJ, Watson WR, Fitzpatrick JM, O'Connell PR (2004) Critical involvement of stressactivated mitogen-activated protein kinases in the regulation of intracellular adhesion molecule-1 in serosal fibroblasts isolated from patients with Crohn's disease. J Am Coll Surg 199:234-42
7. Benn PA (1985) Chromosome translocations in fibroblast cultures derived from patients with Werner's syndrome. Am J Hum Genet 37:221-23
8. Bird J, Ostler EL, Faragher RG (2003) Can we say that senescent cells cause ageing? Exp Gerontol 38:1319-26
9. Blackburn EH (1991) Structure and function of telomeres. Nature 350:569-73
10. Blackburn EH (2000) Telomere states and cell fates. Nature 408:53-56
11. 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 279:349-52
12. Bohr VA (2005) Deficient DNA repair in the human progeroid disorder, Werner syndrome. Mutat Res 577:252-59
13. Bohr VA, Metter EJ, Harrigan JA, Von Kobbe C, Liu JL, Gray MD, Majumdar A, Wilson DM, Seidman MM (2004) Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients. Mech Ageing Dev 125:491-96
14. Brosh RM, Waheed J, Sommers JA (2002) Biochemical characterization of the DNA substrate specificity of Werner syndrome helicase. J Biol Chem 277:23236-45
15. Brown WT, Kieras FJ, Houck GE, Dutkowski R, Jenkins EC (1985) A comparison of adult and childhood progerias: Werner syndrome and Hutchinson-Gilford progeria syndrome. Adv Exp Med Biol 190:229-44
16. Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace AJ (1999) Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18:6845-54
17. Campisi J (2000) Cancer, aging and cellular senescence. In Vivo 14:183-88
18. Castro E, Ogburn CE, Hunt KE, Tilvis R, Louhija J, Penttinen R, Erkkola R, Panduro A, Riestra R, Piussan C, Deeb SS, Wang L, Edland SD, Martin GM, Oshima J (1999) Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians. Am J Med Genet 82:399-403
19. Castro E, Edland SD, Lee L, Ogburn CE, Deeb SS, Brown G, Panduro A, Riestra R, Tilvis R, Louhija J, Penttinen R, Erkkola R, Wang L, Martin GM, Oshima J (2000) Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis. Am J Med Genet 95:374-80
20. Chabaud-Riou M, Firestein GS (2004) Expression and activation of mitogen-activated protein kinase kinases-3 and -6 in rheumatoid arthritis. Am J Pathol 164:177-84
21. Chang S (2005) A mouse model of Werner Syndrome: what can it tell us about aging and cancer? Int J Biochem Cell Biol 37:991-99
22. Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, De Pinho RA (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36:877-82
23. Cheng RZ, Murano S, Kurz B, Shmookler Reis RJ (1990) Homologous recombination is elevated in some Werner-like syndromes but not during normal in vitro or in vivo senescence of mammalian cells. Mutat Res 237:259-69
24. Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, De Pinho RA (1999) p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97:527-38
25. Choi D, Whittier PS, Oshima J, Funk WD (2001) Telomerase expression prevents replicative senescence but does not fully reset mRNA expression patterns in Werner syndrome cell strains. FASEB J 15:1014-20
26. Constantinou A, Tarsounas M, Karow JK, Brosh RM, Bohr VA, Hickson ID, West SC (2000) Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep 1:80-84
27. Crabbe L, Verdun RE, Haggblom CI, Karlseder J (2004) Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306:1951-53
28. Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci USA 95:10614-19
29. D'Adda Di Fagagna F, 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 426:194-98
30. Davis T, Kipling D (2005) Telomeres and telomerase biology in vertebrates: progress towards a non-human model for replicative senescence and ageing. Biogerontology 6:371-85
31. Davis T, Kipling D (2006) Werner Syndrome as an example of inflamm-ageing: possible therapeutic opportunities for a progeroid syndrome? Rejuv Res 9:402-07
32. Davis T, Baird DM, Haughton MF, Jones CJ, Kipling D (2005) Prevention of accelerated cell aging in Werner Syndrome using a p38 mitogen-activated protein kinase inhibitor. J Gerontol A Biol Sci Med Sci 60:1386-93
33. Davis T, Haughton MF, Jones CJ, Kipling D (2006) Prevention of accelerated cell ageing in Werner Syndrome. Ann NY Acad Sci 1067:243-47
34. Davis T, Wyllie FS, Rokicki MJ, Bagley MC, Kipling D (2007) The role of cellular senescence in Werner syndrome: towards therapeutic intervention in human premature ageing. Ann NY Acad Sci 1100:455-69
35. De Lange T (2004) T-loops and the origin of telomeres. Nat Rev Mol Cell Biol 5:323-29
36. De Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100-10
37. Deng Q, Liao R, Wu BL, Sun P (2004) High intensity ras signaling induces premature senescence by activating p38 pathway in primary human fibroblasts. J Biol Chem 279:1050-59
38. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Levy N (2003) Lamin A truncation in Hutchinson-Gilford progeria. Science 300:2055
39. Dumont P, Royer V, Pascal T, Dierick JF, Chainiaux F, Frippiat C, De Magalhaes JP, Eliaers F, Remacle J, Toussaint O (2001) Growth kinetics rather than stress accelerate telomere shortening in cultures of human diploid fibroblasts in oxidative stress-induced premature senescence. FEBS Lett 502:109-12
40. Elli R, Chessa L, Antonelli A, Petrinelli P, Ambra R, Marcucci L (1996) Effects of topoisomerase II inhibition in lymphoblasts from patients with progeroid and "chromosome instability" syndromes. Cancer Genet Cytogenet 87:112-16
41. Faragher RGA, Kill IR, Hunter JA, Pope FM, Tannock C, Shall S (1993) The gene responsible for Werner syndrome may be a cell division "counting" gene. Proc Natl Acad Sci USA 90:12030-34
42. Force T, Kuida K, Namchuk M, Parang K, Kyriakis JM (2004) Inhibitors of protein kinase signaling pathways: emerging therapies for cardiovascular disease. Circulation 109:1196-1205
43. Forsyth NR, Evans AP, Shay JW, Wright WE (2003) Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell 2:235-43
44. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244-54
45. Fry M, Loeb LA (1999) Human Werner Syndrome DNA helicase unwinds tetrahelical structures of the fragile X syndrome repeat sequence d (CGG) n. J Biol Chem 274:12797-802
46. Fujiwara Y, Higashikawa T, Tatsumi M (1977) A retarded rate of DNA replication and normal level of DNA repair in Werner's syndrome fibroblasts in culture. J Cell Physiol 92:365-74
47. Fukuchi K, Martin GM, Monnat RJ (1989) Mutator phenotype of Werner syndrome is characterized by extensive deletions. Proc Natl Acad Sci USA 86:5893-97
48. Funk WD, Wang CK, Shelton DN, Harley CB, Pagon GD, Hoeffler WK (2000) Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. Exp Cell Res 258:270-78
49. Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte PA, Gotteland JP (2005) Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl) acetonitrile inhibitors of the c-Jun. N-terminal kinase. J Med Chem 48:4596-607
50. Garfinkel S, Brown S, Wessendorf JHM, Maciag T (1994) Post-transcriptional regulation of interleukin 1 in various strains of young and senescent human umbilical vein endothelial cells. Proc Natl Acad Sci USA 91:1559-63
51. Gebhart E, Bauer R, Raub U, Schinzel M, Ruprecht KW, Jonas JB (1988) Spontaneous and induced chromosomal instability in Werner syndrome. Hum Genet 80:135-39
52. Godl K, Daub H (2004) Proteomic analysis of kinase inhibitor selectivity and function. Cell Cycle 3:393-95
53. Goldstein DM, Gabriel T (2005) Pathway to development of p38 MAP kinase. A review of ten chemotypes selected for development. Curr Top Med Chem 5:1017-29
54. Goldstein DM, Alfredson T, Bertrand J, Browner MF, Clifford K, Dalrymple SA, Dunn J, Freire-Moar J, Harris S, Labadie SS, La Fargue J, Lapierr, JM, Larrabee S, Li F, Papp E, McWeeney D, Ramesha C, Roberts R, Rotstein D, San Pablo B, Sjogren EB, So OY, Talamas FX, Tao W, Trejo A, Villasenor A, Welch M, Welch T, Weller P, Whiteley PE, Young K, Zipfel S (2006) Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2, 3-dihydroxypropoxy) phe nyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase. J Med Chem 49:1562-75
55. Gorgoulis VG, Pratsinis H, Zacharatos P, Demoliou C, Sigala F, Asimacopoulos PJ, Papavassiliou AG, Kletsas D (2005) p53-dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions. Lab Invest 85:502-11
56. Goto M, Miller RW, Ishikawa Y, Sugano H (1996) Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 5:236-46
57. Goto M (1997) Hierarchical deterioration of body systems in Werner's syndrome: implications for normal ageing. Mech Ageing Dev 98:239-54
58. 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 97:503-14
59. Haq R, Brenton JD, Takahashi M, Finan D, Finkielsztein A, Damaraju S, Rottapel R, Zanke B (2002) Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescence. Cancer Res 62:5076-82
60. Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458-60
61. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC (1990) Telomere reduction in human colorectal carcinoma and with ageing. Nature 346:866-68
62. Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67-77
63. Hentze MW, Kulozik AE (1999) A perfect message: RNA surveillance and nonsense-mediated decay. Cell 96:307-10
64. Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311:1257
65. Hickson ID (2003) RecQ helicases: caretakers of the genome. Nat Rev Cancer 3:169-78
66. Hisama FM, Chen YH, Meyn MS, Oshima J, Weissman SM (2000) WRN or telomerase constructs reverse 4-nitroquinoline 1-oxide sensitivity in transformed Werner syndrome fibroblasts. Cancer Res 60:2372-76
67. Hockemeyer D, Sfeir AJ, Shay JW, Wright WE, De Lange T (2005) POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end. EMBO J 24:2667-78
68. Hoehn H, Bryant EM, Au K, Norwood TH, Boman H, Martin GM (1975) Variegated translocation mosaicism in human skin fibroblast cultures. Cytogenet Cell Genet 15:282-98
69. Hoeijmakers JH (2001) DNA repair mechanisms. Maturitas 38:17-22
70. Hofer AC, Tran RT, Aziz OZ, Wright W, Novelli G, Shay J, Lewis M (2005) Shared phenotypes among segmental progeroid syndromes suggest underlying pathways of aging. J Gerontol A Biol Sci Med Sci 60:10-20
71. Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P, Naumann M (2004) Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J 18:1550-52
72. Hollenbach E, Vieth M, Roessner A, Neumann M, Malfertheiner P, Naumann M (2005) Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn disease. J Biol Chem 280:14981-88
73. Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn, T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, Von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J (2006) The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat 27:558-67
74. Huot J, Houle F, Marceau F, Landry J (1997) Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ Res 80:383-92
75. Iwasa H, Han J, Ishikawa F (2003) Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway. Genes Cells 8:131-44
76. James SE, Faragher RGA, Burke JF, Shall S, Mayne LV (2000) Werner's syndrome T lymphocytes display a normal in vitro life-span. Mech Ageing Dev 121:139-49
77. Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev 12:36-44
78. Johnson FB, Marciniak RA, McVey M, Stewart SA, Hahn WC, Guarente L (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. EMBO J 20:905-13
79. Kamath-Loeb AS, Loeb LA, Johansson E, Burgers PM, Fry M (2001) Interactions between the Werner syndrome helicase and DNA polymerase delta specifically facilitate copying of tetraplex and hairpin structures of the d (CGG) n trinucleotide repeat sequence. J Biol Chem 276:16439-46
80. Karlseder J, Smogorzewska A, De Lange T (2002) Senescence induced by altered telomere state, not telomere loss. Science 295:2446-49
81. Kashino G, Kodama S, Nakayama Y, Suzuki K, Fukase K, Goto M, Watanabe M (2003) Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells. Free Radic Biol Med 35:438-43
82. Keys B, Serra V, Saretzki G, Von Zglinicki T (2004) Telomere shortening in human fibroblasts is not dependent on the size of the telomeric-3'-overhang. Aging Cell 3:103-09
83. Kill IR, Faragher RGA, Lawrence K, Shall S (1994) The expression of proliferation-dependent antigens during the lifespan of normal and progeroid human fibroblasts in culture. J Cell Sci 107:571-79
84. Kim G Y, Mercer SE, Ewton DZ, Yan Z, Jin K, Friedman E (2002) The stress-activated protein kinases p38 alpha and JNK1 stabilize p21 (Cip1) by phosphorylation. J Biol Chem 277:29792-802
85. Kipling D, Davis T, Ostler EL, Faragher RG (2004) What can progeroid syndromes tell us about human aging? Science 305:1426-31
86. Krtolica AR, Campisi J (2002) Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol 34:1401-14
87. Kumar S, Millis AJ, Baglioni C (1992) Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proc Natl Acad Sci USA 89:4683-87
88. Kumar S, Vinci JM, Millis AJ, Baglioni C (1993) Expression of interleukin-1 alpha and beta in early passage fibroblasts from aging individuals. Exp Gerontol 28:505-13
89. Kuningas M, Slagboom PE, Westendorp RG, Van Heemst D (2006). Impact of genetic variations in the WRN gene on age related pathologies and mortality. Mech Ageing Dev 127:307-13
90. Lans H, Hoeijmakers JHJ (2006) Ageing nucleus gets out of shape. Nature 440:32-34
91. Lavigne P, Benderdour M, Lajeunesse D, Shi Q, Fernandes JC (2004) Expression of ICAM-1 by osteoblasts in healthy individuals and in patients suffering from osteoarthritis and osteoporosis. Bone 35:463-70
92. Liu M, Xin Z, Clampit JE, Wang, S, Gum RJ, Haasch DL, Trevillyan JM, Abad-Zapatero C, Fry EH, Sham HL, Liu G (2006) Synthesis and SAR of 1, 9-dihydro-9-hydroxypyrazolo[3, 4-b] quinolin-4-ones as novel, selective c-Jun. N-terminal kinase inhibitors. Bioorg Med Chem Lett 16:2590-94
93. Maier JA, Voulalas P, Roeder D, Maciag T (1990) Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. Science 249:1570-74
94. Martin GM, Oshima J, Gray MD, Poot M (1999) What geriatricians should know about the Werner syndrome. J Am Geriatr Soc 47:1136-44
95. Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, De Caprio JA, Weinberg RA, Stewart SA, Hahn WC (2003) Telomerase maintains telomere structure in normal human cells. Cell 114:241-53
96. Melcher R, Von Golitschek R, Steinlein C, Schindler D, Neitzel H, Kainer K, Schmid M, Hoehn H (2000) Spectral karyotyping of Werner syndrome fibroblast cultures. Cytogenet Cell Genet 91:180-85
97. Miklossy J, Doudet DD, Schwab C, Yu S, McGeer EG, McGeer PL (2006) Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys. Exp Neurol 197:275-83
98. Mohaghegh P, Karow JK, Brosh RM, Bohr VA, Hickson ID (2001) The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res 29:2843-49
99. Moser MJ, Holley WR, Chatterjee A, Mian IS (1997) The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains. Nucleic Acids Res 25:5110-18
100. Moser MJ, Oshima J, Monnat RJ (1999) WRN mutations in Werner syndrome. Hum Mutat 13:271-79
101. Moser MJ, Kamath-Loeb AS, Jacob JE, Bennett SE, Oshima J, Monnat RJ (2000) WRN helicase expression in Werner syndrome cell lines. Nucleic Acids Res 28:648-54
102. Muller FB, Tsianakas A, Kuwert C, Korge BP, Hunzelmann N (2005) A novel compound heterozygous mutation in Werner syndrome results in WRN transcript decay. Br J Dermatol 152:1030-32
103. Murano S, Nakazawa A, Saito I, Masuda M, Morisaki N, Akikusa B, Tsuboyama T, Saito Y (1997) Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome. Gerontology 43 Suppl 1:43-52
104. O'Hare MJ, Bond J, Clarke C, Takeuchi Y, Atherton AJ, Berry C, Moody J, Silver AR, Davies DC, Alsop AE, Neville AM, Jat PS (2001) Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proc Natl Acad Sci USA 98, 646-51
105. Ogburn CE, Oshima J, Poot M, Chen R, Hunt KE, Gollahon KA, Rabinovitch PS, Martin GM (1997) An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants. Hum Genet 101:121-25
106. Okada M, Goto M, Furuichi Y, Sugimoto M (1998) Differential effects of cytotoxic drugs on mortal and immortalized B-lymphoblastoid cell lines from normal and Werner's syndrome patients. Biol Pharm Bull 21:235-39
107. Olovnikov AM (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 41:181-90
108. Opresko PL, Von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA (2002) Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 277:41110-19
109. Opresko PL, Cheng WH, Von Kobbe C, Harrigan JA, Bohr VA (2003) Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 24:791-802
110. 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 14:763-74
111. Opresko PL, Mason PA, Podell ER, Lei M, Hickson ID, Cech TR, Bohr VA (2005) POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J Biol Chem 280:32069-80
112. Orren DK, Theodore S, Machwe A (2002) The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 41:13483-88
113. Ostler EL, Wallis C V, Sheerin AN, Faragher RGA (2002) A model for the phenotypic presentation of Werner's syndrome. Exp Gerontol 37:285-92
114. Ouellette MM, McDaniel LD, Wright WE, Shay JW, Schultz RA (2000) The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes. Hum Mol Genet 9:403-11
115. Pagano G, Zatterale A, Degan P, D'Ischia M, Kelly FJ, Pallardo F V, Calzone R, Castello G, Dunster C, Giudice A, Kilinc Y, Lloret A, Manini P, Masella R, Vuttariello E, Warnau M (2005a) In vivo prooxidant state in Werner syndrome (WS): results from three WS patients and two WS heterozygotes. Free Radic Res 39:529-33
116. Pagano G, Zatterale A, Degan P, D'Ischia M, Kelly FJ, Pallardo F V, Kodama S (2005b) Multiple involvement of oxidative stress in Werner syndrome phenotype. Biogerontology 6:233-43
117. Pichierri P, Franchitto A (2004) Werner syndrome protein, the MRE11 complex and ATR: menage-a-trois in guarding genome stability during DNA replication? Bioessays 26:306-13
118. Postiglione A, Soricelli A, Covelli EM, Iazzetta N, Ruocco A, Milan G, Santoro L, Alfano B, Brunett A (1996) Premature aging in Werner's syndrome spares the central nervous system. Neurobiol Aging 17:325-30
119. Poot M, Gollahon KA, Rabinovitch PS (1999) Werner syndrome lymphoblastoid cells are sensitive to camptothecin-induced apoptosis in S-phase. Hum Genet 104:10-14
120. Poot M, Gollahon KA, Emond MJ, Silber JR, Rabinovitch PS (2002) Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype. FASEB J 16:757-58
121. Prince PR, Ogburn CE, Moser MJ, Emond MJ, Martin GM, Monnat RJ (1999) Cell fusion corrects the 4-nitroquinoline 1-oxide sensitivity of Werner syndrome fibroblast cell lines. Hum Genet 105:132-38
122. Rodriguez-Lopez AM, Jackson DA, Iborra F, Cox LS (2002) Asymmetry of DNA replication fork progression in Werner's syndrome. Aging Cell 1:30-39
123. Rubin H (2002) The disparity between human cell senescence in vitro and lifelong replication in vivo. Nat Biotechnol 20:675-81
124. Rudolph KL, Chan S, Lee HW, Blasco M, Gottlieb GJ, Greider C, De Pinho RA (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96:701-12
125. Saintigny Y, Makienko K, Swanson C, Emond MJ, Monnat RJ (2002) Homologous recombination resolution defect in werner syndrome. Mol Cell Biol 22:6971-78
126. Saito H, Hammond AT, Moses RE (1995) The effect of low oxygen tension on the in vitro-replicative life span of human diploid fibroblast cells and their transformed derivatives. Exp Cell Res 217:272-79
127. Salk D (1982) Werner's syndrome: a review of recent research with an analysis of connective tissue metabolism, growth control of cultured cells, and chromosomal aberrations. Hum Genet 62:1-5
128. Salk D, Au K, Hoehn H, Martin GM (1981a) Cytogenetics of Werner's syndrome cultured skin fibroblasts: variegated translocation mosaicism. Cytogenet Cell Genet 30:92-107
129. Salk D, Au K, Hoehn H, Martin GM (1981b) Effects of radical-scavenging enzymes and reduced oxygen exposure on growth and chromosome abnormalities of Werner syndrome cultured skin fibroblasts. Hum Genet 57:269-75
130. Salk D, Bryant E, Au K, Hoehn H, Martin GM (1981c) Systematic growth studies, cocultivation, and cell hybridization studies of Werner syndrome cultured skin fibroblasts. Hum Genet 58:310-16
131. Saretzki G, Sitte N, Merkel U, Wurm RE, Von Zglinicki T (1999) Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments. Oncogene 18:5148-58
132. Satoh M, Imai M, Sugimoto M, Goto M, Furuichi Y (1999) Prevalence of Werner's syndrome heterozygotes in Japan. Lancet 353:1766
133. Satyanarayana A, Greenberg RA, Schaetzlein S, Buer J, Masutomi K, Hahn WC, Zimmermann S, Martens U, Manns MP, Rudolph KL (2004) Mitogen stimulation cooperates with telomere shortening to activate DNA damage responses and senescence signaling. Mol Cell Biol 24:5459-547
134. Schnabl B, Purbeck CA, Choi YH, Hagedorn CH, Brenner D (2003) Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype. Hepatology 37:653-64
135. Schonberg S, Niermeijer MF, Bootsma D, Henderson E, German J (1984) Werner's syndrome: proliferation in vitro of clones of cells bearing chromosome translocations. Am J Hum Genet 36:387-97
136. Schulz VP, Zakian VA, Ogburn CE, McKay J, Jarzebowicz AA, Edland SD, Martin GM (1996) Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells. Hum Genet 97:750-54
137. Shelton DN, Chang E, Whittier PS, Choi D, Funk WD (1999) Microarray analysis of replicative senescence. Curr Biol 9:939-45
138. Shen J, Loeb LA (2001) Unwinding the molecular basis of the Werner syndrome. Mech Ageing Dev 122:921-44
139. Spillare EA, Robles AI, Wang XW, Shen JC, Yu CE, Schellenberg GD, Harris CC (1999) p53-mediated apoptosis is attenuated in Werner syndrome cells. Genes Dev 13:1355-60
140. Stansel RM, De Lange T, Griffith JD (2001) T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang. EMBO J 20:5532-40
141. Stewart SA, Ben-Porath I, Carey VJ, O'Connor BF, Hahn WC, Weinberg RA (2003) Erosion of the telomeric single-strand overhang at replicative senescence. Nat Genet 33:492-96
142. Suzuki T, Shiratori M, Furuichi Y, Matsumoto T (2001) Diverged nuclear localization of Werner helicase in human and mouse cells. Oncogene 20:2551-58
143. Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum R, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM (2006) Aminopyridine-based c-Jun. N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem 49:3563-80
144. Tahara H, Tokutake Y, Maeda S, Kataoka H, Watanabe T, Satoh M, Matsumoto T, Sugawara M, Ide T, Goto M, Furuichi Y, Sugimoto M (1997) Abnormal telomere dynamics of B-lymphoblastoid cell strains from Werner's syndrome patients transformed by Epstein-Barr virus. Oncogene 15:1911-20
145. Tollefsbol TO, Cohen HJ (1984) Werner's syndrome: An underdiagnosed disorder resembling premature aging. Age 7:75-88
146. Van Steensel B, Smogorzewska A, De Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92:401-13
147. Vaziri H, Benchimol S (1996) From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging. Exp Gerontol 31:295-301
148. Vaziri H, Benchimol S (1998) Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol 8:279-82
149. Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci USA 91:9857-60
150. Vainer B (2005) Intercellular adhesion molecule-1 (ICAM-1) in ulcerative colitis: presence, visualization, and significance. Inflamm Res 54:313-27
151. Van De Berg JS, Rose MA, Haywood-Reid PL, Rudolph R, Payne WG, Robson MC (2005) Cultured pressure ulcer fibroblasts show replicative senescence with elevated production of plasmin, plasminogen activator inhibitor-1, and transforming growth factor-beta1. Wound Repair Regen. 13:76-83
152. Verdun RE, Karlseder J (2006) The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127:709-20
153. Vijg J, Calder RB (2004) Transcripts of aging. Trends Genet 20:221-24
154. Von Zglinicki T, Burkle A, Kirkwood TB (2001) Stress, DNA damage and ageing - an integrative approach. Exp Gerontol 36:1049-62
155. Wang W, Chen JX, Liao R, Deng Q, Zhou JJ, Huang S, Sun P (2002) Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence. Mol Cell Biol 22:3389-3403
156. Werner O (1904). On cataract associated in conjunction with scleroderma. Doctoral Dissertation, Kiel University, Schmidt and Klaunig, Kiel
157. Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RGA, Kipling D (2000) Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nat Genet 24:16-17
158. Yamabe Y, Sugimoto M, Satoh M, Suzuki N, Sugawara M, Goto M, Furuichi Y (1997) Downregulation of the defective transcripts of the Werner's syndrome gene in the cells of patients. Biochem Biophys Res Commun 236:151-54
159. Yokote K, Honjo S, Kobayashi K, Fujimoto M, Kawamura H, Mori S, Saito Y (2004) Metabolic improvement and abdominal fat redistribution in Werner syndrome by pioglitazone. J Am Geriatr Soc 52:1582-83
160. Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD (1996) Positional cloning of the Werner's syndrome gene. Science 272:258-62
161. Zou Y, Sfeir A, Gryaznov SM, Shay JW, Wright WE (2004) Does a sentinel or a subset of short telomeres determine replicative senescence? Mol Biol Cell 15:3709-18