A novel werner syndrome mutation: Pharmacological treatment by read-through of nonsense mutations and epigenetic therapies

Epigenetics

Volumn 10, Issue 4, 2015, Pages 329-341

  Agrelo, Ruben ^a   Sutz, Miguel Arocena ^a   Setien, Fernando ^b   Aldunate, Fabian ^a   Esteller, Manel ^b   Da Costa, Valeria ^a   Achenbach, Ricardo ^c  

^a INSTITUT PASTEUR DE MONTEVIDEO   (Uruguay)

^b BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

^c HOSPITAL DURAND   (Argentina)

Author keywords

Epigenetics; Methylation; Mutation; PTC read through therapy; Werner syndrome

Indexed keywords

AMINOGLYCOSIDE; ANTIBIOTIC G 418; ATALUREN; MESSENGER RNA; STREPTOMYCIN; WERNER SYNDROME PROTEIN; OXADIAZOLE DERIVATIVE; PROTEIN SYNTHESIS INHIBITOR; STOP CODON;

ALOPECIA; APOPTOSIS; ARGENTINIAN; ARTICLE; CASE REPORT; CHROMOSOME DAMAGE; CLONING; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DNA DAMAGE; DNA DETERMINATION; DNA METHYLATION; DNA REPLICATION; EPIGENETICS; EPSTEIN BARR VIRUS; HUMAN; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; LEG ULCER; LYMPHOBLASTOID CELL LINE; MALE; NICK END LABELING; NONSENSE MUTATION; PHENOTYPE; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; STOP CODON; TUMOR SUPPRESSOR GENE; WERNER SYNDROME; CELL CULTURE; DRUG EFFECTS; FEMALE; GENETIC EPIGENESIS; GENETICS; HUMAN CHROMOSOME; MUTATION; PREMATURE AGING; PROMOTER REGION;

AGING, PREMATURE; AMINOGLYCOSIDES; APOPTOSIS; CELLS, CULTURED; CHROMOSOMES, HUMAN; CODON, NONSENSE; DNA DAMAGE; DNA METHYLATION; DNA REPLICATION; EPIGENESIS, GENETIC; FEMALE; HUMANS; MALE; MUTATION; OXADIAZOLES; PROMOTER REGIONS, GENETIC; PROTEIN SYNTHESIS INHIBITORS; WERNER SYNDROME;

EID: 84927710967     PISSN: 15592294     EISSN: 15592308     Source Type: Journal    
DOI: 10.1080/15592294.2015.1027853     Document Type: Article

References (76)

1. Epstein CJ, Martin GM, Schultz AL, Motulsky AG. Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 1966; 45:177-21; PMID:5327241
2. Salk D. 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 1982; 62:1-5; PMID:6759366; http://dx.doi.org/10.1007/BF00295598
3. Goto M. Hierarchical deterioration of body systems in Werner’s syndrome: implications for normal ageing. Mech Ageing Dev 1997; 98:239-54; PMID:9352493
4. Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr. Spectrum and risk of neoplasia in Werner syndrome: a systematic review. PLoS One 2013; 8(4):e59709; PMID:23573208; http://dx.doi.org/10.1371/journal.pone.0059709
5. Goto M, Miller RW, Ishikawa Y, Sugano H. Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 1996; 5:239-46; PMID:8722214
6. Yamamoto K, Imakiire A, Miyagawa N, Kasahara T. A report of two cases of Werner’s syndrome and review of the literature. J Orthop Surg (Hong Kong) 2003; 11:224-33.
7. Salk D. 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 1982; 62:1-5; PMID:6759366; http://dx.doi.org/10.1007/BF00295598.
8. Salk D, Au K, Hoehn H, Martin GM. Cytogenetics of Werner’s syndrome cultured skin fibroblasts: variegated translocation mosaicism. Cytogenet Cell Genet 1981; 30:92-107; PMID:7273860
9. Gebhart E, Bauer R, Raub U, Schinzel M, Ruprecht KW, Jonas JB. Spontaneous and induced chromosomal instability in Werner syndrome. Hum Genet 1988; 80:135-9; PMID:2459043; http://dx.doi.org/10.1007/BF00702855.
10. Honma M, Tadokoro S, Sakamoto H, Tanabe H, Sugimoto M, Furuichi Y, Satoh T, Sofuni T, Goto M, Hayashi M. Chromosomal instability in B-lymphoblasotoid cell lines from Werner and Bloom syndrome patients. Mutat Res 2002; 26; 15-24; PMID:12297140
11. Poot M, Gollahon KA, Emond MJ, Silber JR, Rabinovitch PS. Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype. FASEB J 2002; 16:757-8; PMID:11978740
12. Ogburn CE, Oshima J, Poot M, Chen R, Hunt KE, Gollahon KA, Rabinovitch PS, Martin GM. An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants. Hum Genet 1997; 101:121-5; PMID:9402954; http://dx.doi.org/10.1007/s004390050599
13. Poot M, Gollahon KA, Rabinovitch PS. Werner syndrome lymphoblastoid cells are sensitive to camptothecin-induced apoptosis in S-phase. Hum Genet 1999; 104:10-14; PMID:10071186; http://dx.doi.org/10.1007/s004390050903
14. Poot M, Yom JS, Whang SH, Kato JT, Gollahon KA, Rabinovitch PS.Werner syndrome cells are sensitive to DNA cross-linking drugs. FASEB J 2001; 15:1224-6; PMID:11344095
15. Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, et al. Positional cloning of the Werner’s syndrome gene. Science 1996; 272:258-62; PMID:8602509
16. Larsen NB, Hickson ID RecQ Helicases: Conserved guardians of genomic integrity. AdvExp Med Biol 2013; 767:161-84; PMID:23161011; http://dx.doi.org/10.1007/978-1-4614-5037-5_8
17. Rossi ML, Ghosh AK, Bohr VA. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair 2010; 9:331-44; PMID:20075015; http://dx.doi.org/10.1016/j.dnarep.2009.12.011
18. Yu CE, Oshima J, Wijsman EM, Nakura J, Miki T, Piussan C, Matthews S, Fu YH, Mulligan J, Martin GM, et al. Mutations in the consensus helicase domains of the Werner syndrome gene. Werner’s Syndrome Collaborative Group. Am J Hum Genet 1997; 60:330-41; PMID:9012406
19. Gray MD, Shen JC, Kamath-Loeb AS, Blank A, Sopher BL, Martin GM, Oshima J, Loeb LA. The Werner syndrome protein is a DNA helicase. Nat Genet 1997 Sep; 17(1):100-3; PMID:9288107; http://dx.doi.org/10.1038/ng0997-100
20. Suzuki N, Shimamoto A, Imamura O, Kuromitsu J, Kitao S, Goto M, Furuichi Y. DNA helicase activity in Werner’s syndrome gene product synthesized in a baculovirus system. Nucleic Acids Res 1997; 25(15):2973-8; PMID:9224595; http://dx.doi.org/10.1093/nar/25.15.2973
21. Huang S, Li B, Gray MD, Oshima J, Mian IS, Campisi J. The premature ageing syndrome protein, WRN, is a 3’–>5’ exonuclease. Nat Genet 1998; 20 (2):114-6; PMID:9771700; http://dx.doi.org/10.1038/2410
22. Spillare EA, Robles AI, Wang XW, Shen JC, Yu CE, Schellenberg GD, Harris CC. p53-mediated apoptosis is attenuated in Werner syndrome cells. Genes Dev 1999; 13:1355-60.
23. Crabbe L, Jauch A, Naeger CM, Holtgreve-Grez H, Karlseder J. Telomere dysfunction as a cause of genomic instability in Werner syndrome. ProcNatlAcadSci U S A 2007 13; 104:2205-10; PMID:17284601; http://dx.doi.org/10.1073/pnas.0609410104
24. Matsumoto T, Shimamoto A, Goto M, Furuichi Y. Impaired nuclear localization of defective DNA helicases in Werner’s syndrome. Nat Genet 1997; 16:335-6; PMID:9241267; http://dx.doi.org/10.1038/ng0897-335
25. vonKobbe C, Bohr VA. A nucleolar targeting sequence in the Werner syndrome protein resides within residues 949–1092. J Cell Sci 2002; 115:3901-7; PMID:12244128
26. Marciniak RA, Lombard DB, Johnson FB, Guarente L. Nucleolar localization of the Werner syndrome protein in human cells. ProcNatlAcadSci U S A 1998 9; 95:6887-92; PMID:9618508; http://dx.doi.org/10.1073/pnas.95.12.6887
27. Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, et al. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat 2006; 27:558-67; PMID:16673358; http://dx.doi.org/10.1002/humu. 20337
28. Friedrich K, Lee L, Leistritz DF, Nürnberg G, Saha B, Hisama FM, Eyman DK, Lessel D, Nürnberg P, Li C, et al. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations. Hum Genet 2010; 128:103-11; PMID:20443122; http://dx.doi.org/10.1007/s00439-010-0832-5
29. Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, et al. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat 2006; 27: 558-67; PMID:16673358; http://dx.doi.org/10.1002/humu.20337
30. Goto M, Imamura O, Kuromitsu J, Matsumoto T, Yamabe Y, Tokutake Y, Suzuki N, Mason B, Drayna D, Sugawara M, et al. Analysis of helicase gene mutations in Japanese Werner’s syndrome patients.. Hum Genet 1997; 99 (2):191-3; PMID:9048918; http://dx.doi.org/10.1007/s004390050336
31. Yamabe Y, Sugimoto M, Satoh M, Suzuki N, Sugawara M, Goto M, Furuichi Y. Down-regulation of the defective transcripts of the Werner’s syndrome gene in the cells of patients. Biochem Biophys Res Commun 1997; 236:151-54; PMID:9223443; http://dx.doi.org/10.1006/bbrc.1997.6919
32. Wang L, Hunt KE, Martin GM, Oshima J. Structure and function of the human Werner syndrome gene promoter: evidence for transcriptional modulation. Nucleic Acids Res 1998; 26:3480-5; PMID:9671808
33. Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, et al. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A 2006; 103:8822-7; PMID:16723399; http://dx.doi.org/10.1073/pnas.0600645103
34. Bidou L, Allamand V, Rousset JP, Namy O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med 2012; 18:679-88; PMID:23083810; http://dx.doi.org/10.1016/j.molmed.2012.09.008
35. Palombo M; Monroy S, Achenbach RE. Síndrome de Werner: Dos nuevos casos. Rev Argent Dermatol 2010; 91: 1-9.
36. Muftuoglu M, Oshima J, von Kobbe C, Cheng WH, Leistritz DF, Bohr VA. The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis. Hum Genet 2008; 124:369-77; PMID:18810497; http://dx.doi.org/10.1007/s00439-008-0562-0
37. Yeong EK, Yang CC. Chronic leg ulcers in Werner’s syndrome. Br J Plast Surg 2004; 57:86-8; PMID:14672683; http://dx.doi.org/10.1016/j.bjps.2003.10.011
38. Goto M, Yamabe Y, Shiratori M, Okada M, Kawabe T, Matsumoto T, Sugimoto M, Furuichi Y. Immunological diagnosis of Werner syndrome by down-regulated and truncated gene products. HumGenet 1999; 105:301-7; PMID:10543396
39. Agrelo R. Epigenetic Silencing of Progeroid Syndromes. In Epigenetics of Aging. Tollefsbol, TO. ed. 1sted. Springer Verlag, New York, 2010.
40. Keeling KM, Xue X, Gunn G, Bedwell DM. Therapeutics based on stop codon readthrough. Annu Rev Genomics Hum Genet 2014; 15:371-94; PMID:24773318.
41. Rodríguez-López AM, Jackson DA, Iborra F, Cox LS. Asymmetry of DNA replication fork progression in Werner’s syndrome. Aging Cell 2002; 1:30-9; PMID:12882351.
42. Fraga MF, Agrelo R, Esteller M. Cross-talk between aging and cancer: the epigenetic language. Ann N Y Acad Sci 2007; 1100:60-74; PMID:17460165; http://dx.doi.org/10.1196/annals.1395.005.
43. Kim J, Kim Y-J, Issa JP. Aging and DNAmethylation. Curr Chem Biol 2009; 3:321-9.
44. Bachrati CZ, Hickson ID. RecQhelicases:suppressors of tumorigenesis and premature aging. Biochem J 2003; 15:577-606; PMID:12803543
45. Esteller M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 2007 15; 16 Spec No 1:R50-9; PMID:17613547
46. Christensen BC, Houseman EA, Marsit CJ. Aging and Environmental ExposuresAlter Tissue-Specific DNA MethylationDependent upon CpG Island Context. Plos Genet 2009:5:e1000602.
47. Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C, Greally JM, Barzilai N. Tissue-specific dysregulation of DNAmethylation in aging. Aging Cell 2010; 9: 506-18; PMID:20497131; http://dx.doi.org/10.1111/j.1474-9726.2010.00577.x
48. Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, Zhang N, Liang S, Donehower LA, Issa JP. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 2010; 20:332-40; PMID:20107151
49. Addo BK, Chung W, Shen L, Ittmann M, Wheeler T, Jelinek J, Issa JP. Age-Related DNA Methylation Changes in Normal Human Prostate Tissues. Clin Cancer Res 2007; 13:3796-802; PMID:17606710; http://dx.doi.org/10.1158/1078-0432.CCR-07-0085
50. Koch CM, Suschek CV, Lin Q, Bork S, Goergens M, Joussen S, Pallua N, Ho AD, Zenke M, Wagner W. Specific age-associated DNA methylation changes in human dermal fibroblasts. PLoS One 2011; 6:e16679; PMID:21347436; http://dx.doi.org/10.1158/10.1371/journal.pone.0016679
51. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A 2012; 109:10522-7; PMID:22689993; http://dx.doi.org/10.1158/10.1073/pnas.1120658109
52. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 2005; 102:10604-9; PMID:16009939
53. Goto M, Ishikawa Y, Sugimoto M, Furuichi Y. Werner syndrome: a changing pattern of clinical manifestations in Japan (1917»2008). BiosciTrends 2013; 7:13-22; PMID:23524889
54. Brendel C, Belakhov V, Werner H, Wegener E, Gärtner J, Nudelman I, Baasov T, Huppke P. Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model. J Mol Med (Berl) 2011; 89:389-98.
55. Floquet C, Deforges J, Rousset JP, Bidou L. Rescue of nonsense mutated p53 tumor suppressor gene by aminoglycosides. Nucleic Acids Res 2011; 39:3350-62; PMID:21149266; http://dx.doi.org/10.1093/nar/gkq1277
56. Floquet C, Rousset JP, Bidou L. Readthrough of premature termination codons in the adenomatous polyposis coli gene restores its biological activity in human cancer cells. PLoS One 2011; 6:e24125; PMID:21909382
57. Kuschal C, DiGiovanna JJ, Khan SG, Gatti RA, Kraemer KH. Repair of UV photolesions in xerodermapigmentosum group C cells induced by translational readthrough of premature termination codons. Proc Natl Acad Sci U S A 2013; 110(48):19483-8; PMID:24218596; http://dx.doi.org/10.1073/pnas.1312088110
58. Finkel RS, Flanigan KM, Wong B, Bönnemann C, Sampson J, Sweeney HL, Reha A, Northcutt VJ, Elfring G, Barth J, et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS One 2013; 8:e81302; PMID:24349052; http://dx.doi.org/10.1371/journal.pone.0081302
59. Foster H, Popplewell L, Dickson G. Genetic therapeutic approaches for Duchenne muscular dystrophy. Hum Gene Ther 2012; 23:676-87; PMID:22647146; http://dx.doi.org/10.1089/hum.2012.099
60. Floquet C, Hatin I, Rousset JP, Bidou L. Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin. PLoS Genet 2012; 8: e1002608.
61. Tan L, Narayan SB, Chen J, Meyers GD, Bennett MJ. PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation. J Inherit Metab Dis 2011; 34:443-7.
62. Goldmann T, Overlack N, Wolfrum U, Nagel-Wolfrum K. PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C. Hum Gene Ther 2011; 22:537-47; PMID:21235327; http://dx.doi.org/10.1089/hum.2010.067
63. Wilschanski M, Miller LL, Shoseyov D, Blau H, Rivlin J, Aviram M, Cohen M, Armoni S, Yaakov Y, Pugatsch T, et al. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. Eur Respir J 2011; 38:59-69.
64. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, et al. PTC124 targets genetic disorders caused by nonsensemutations. Nature 2007; 447:87-91; PMID:17450125; http://dx.doi.org/10.1038/nature05756
65. Linde L, Boelz S, Nissim-Rafinia M, Oren YS, Wilschanski M, Yaacov Y, Virgilis D, Neu-Yilik G, Kulozik AE, Kerem E, et al. .Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J Clin Invest 2007; 117:683-92; PMID:17290305; http://dx.doi.org/10.1172/JCI28523
66. Müller FB, Tsianakas A, Kuwert C, Korge BP, Hunzelmann N. A novel compound heterozygous mutation in Werner syndrome results in WRN transcript decay. Br J Dermatol 2005; 152:1030-2; PMID:15888165; http://dx.doi.org/10.1111/j.1365-2133.2005.06483.x
67. Kaneko R, Kawaguchi M, Toyama T, Taguchi Y, Yagi T. Expression levels of Protocadherin-alpha transcripts are decreased by nonsense-mediated mRNA decay with frameshift mutations and by high DNA methylation in their promoter regions. Gene; 2009 430:86-94; PMID:19038318; http://dx.doi.org/10.1016/j.gene.2008.10.018
68. Bhattacharya A, Czaplinski K, Trifillis P, He F, Jacobson A, Peltz SW. Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. RNA 2000; 6:1226-35; PMID:10999600; http://dx.doi.org/10.1017/S1355838200000546
69. Jacobson A, Peltz SW. Tools for turnover: methods for analysis of mRNA stability in eukaryotic cells. Methods 1999; 17:1-2; PMID:10075876; http://dx.doi.org/10.1006/meth.1998.0700
70. Jacobson A, Peltz SW. Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem 1996; 65:693-739; PMID:8811193; http://dx.doi.org/10.1146/annurev.bi.65.070196.003401
71. Peltz SW, Welch EM, Trotta CR, Davis T, Jacobson A. Targeting post-transcriptional control for drug discovery. RNA Biol 2009; 6:329-34. Epub 2009 Jul 7. Review; PMID:19574739
72. Hinzpeter A, Aissat A, de Becdeliévre A, Bieth E, Sondo E, Martin N, Costes B, Costa C, Goossens M, Galietta LJ, et al. Alternative splicing of in-frame exon associated with premature termination codons: implications for readthrough therapies. Hum Mutat 2013; 34:287-91; PMID:23065710; http://dx.doi.org/10.1002/humu.22236
73. Tahara H, Tokutake Y, Maeda S, Kataoka H, Watanabe T, Satoh M, Matsumoto T, Sugawara M, Ide T, Goto M, et al. Abnormal telomere dynamics of B-lymphoblastoid cell strains from Werner’s syndrome patients transformed by Epstein-Barr virus. Oncogene 1997; 15:1911-20; PMID:9365237; http://dx.doi.org/10.1038/sj.onc.1201377
74. Miller G, LipmanM. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A 1973; 70:190-4; PMID:4346033; http://dx.doi.org/10.1073/pnas.70.1.190
75. Ionov Y, Nowak N, Perucho M, Markowitz S, Cowell JK. Manipulation of nonsense mediated decay identifies gene mutations in colon cancer Cells with microsatellite instability. Oncogene 2004; 23:639-45; PMID:14737099; http://dx.doi.org/10.1038/sj.onc.1207178
76. Leeb M, Wutz A. Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. J Cell Biol 2007; 178: 219-229; PMID:17620408; http://dx.doi.org/10.1083/jcb.200612127