Blasco MA. 2002. Telomerase beyond telomeres. Nat Rev Cancer, 2:627–33. Bridger JM, Kill IR. 2004. Aging of Hutchinson-Gilford progeria syndrome ﬁbroblasts is characterised by hyperproliferation and increased apop- tosis. Exp Gerontol, 39:717–24. Brosh RM Jr, Orren DK, Nehlin JO, et al. 1999. Functional and physical interaction between WRN helicase and human replication protein A J Biol Chem, 274:18341–50. Brosh RM Jr, Li JL, Kenny MK, et al. 2000. Replication protein A physi- cally interacts with the Bloom’s syndrome protein and stimulates its helicase activity. J Biol Chem, 275:23500–8. Brosh RM Jr, Karmakar P, Sommers JA, et al. 2001a. p53 modulates the exonuclease activity of Werner syndrome protein. J Biol Chem, 276:35093–102. Brosh RM Jr, Majumdar A, Desai S, et al. 2001b. Unwinding of a DNA triple helix by the Werner and Bloom syndrome helicases. J Biol Chem, 276:3024–30. Brosh RM Jr, von Kobbe C, Sommers JA, et al. 2001c. Werner syndrome protein interacts with human ﬂap endonuclease 1 and stimulates its cleavage activity, EMBO J, 20:5791–801. Brosh RM Jr, Bohr VA. 2002. Roles of the Werner syndrome protein in pathways required for maintenance of genome stability. Exp Gerontol, 37:491–506. Brosh RM Jr, Driscoll HC, Dianov GL, et al. 2002. Biochemical charac- terization of the WRN-FEN-1 functional interaction. Biochemistry, 41:12204–16. Cao H, Hegele RA. 2003. LMNA is mutated in Hutchinson-Gilford pro- geria (MIM 176670) but not in Wiedemann- Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet, 48:271–4. Capell BC, Erdos MR, Madigan JP, et al. 2005. Inhibiting farnesyl- ation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA, 102:12879–84. Chang S, Multani AS, Cabrera NG, et al. 2004. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nature Genetics, 36:877–82. Chen L, Huang S, Lee L, et al. 2003. WRN, the protein deﬁcient in Werner syndrome, plays a critical structural role in optimizing DNA repair. Aging Cell, 2:191–9. Cheng WH, von Kobbe C, Opresko PL, et al. 2003. Werner syndrome protein phosphorylation by abl tyrosine kinase regulates its activity and distribution. Mol Cel. Biol, 23:6385–95. Cheng WH, von Kobbe C, Opresko PL, et al. 2004. Linkage between Wer- ner syndrome protein and the Mre11 complex via Nbs1. J Bio Chem, 279:21169–76. Clarke S, Vogel JP, Deschenes RJ, et al. 1988. Posttranslational modi- ﬁcation of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. Proc Natl Acad Sci, USA, 85:4643–7. Clarke AR, Purdie CA, Harrison DJ, et al. 1993. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature, 362:849−–52. Collado M, Blasco MA, Serrano M. 2007. Cellular senescence in cancer and aging. Cell, 130:223–33. Constantinou A, Tarsounas M, Karow JK, et al. 2000. Werner’s syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep, 1:80–4. Cooper MP, Machwe A, Orren DK, et al. 2000. Ku complex interacts with and stimulates the Werner protein. Genes Dev, 14:907–12. Corrigan DP, Kuszczak D, Rusinol AE, et al. 2005. Prelamin A endo- proteolytic processing in vitro by recombinant Zmpste24. Biochem J, 387:129–38. Cortez D, Guntuku S, Qin J, et al. 2001. ATR and ATRIP: partners in checkpoint signaling. Science, 294:1713–16. Crabbe L, Verdun RE, Haggblom CI, et al. 2004. Defective telomere lag- ging strand synthesis in cells lacking WRN helicase activity. Science, 306:1951–3. Clinical Interventions in Aging 2008:3(3) Werner’s and Hutchinson-Gilford progeria syndromes Csoka AB, Cao H, Sammak PJ, et al. 2004a. Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet, 41:304–8. Csoka AB, English SB, Simkevich CP, et al. 2004b. Genome-scale expression proﬁling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/ mesenchymal defects and accelerated atherosclerosis. Aging Cell, 3:235–43. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. 2003. A DNA damage checkpoint response in telomere-initiated senescence. Nature, 426:194–8. Dahl KN, Scafﬁdi P, Islam MF, et al. 2006. Distinct structural and mechani- cal properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA, 103:10271–6. Dai Q, Choy E, Chiu V, et al. 1998. Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J Biol Chem, 273:15030–4. De Lange T. 2002. Protection of mammalian telomeres. Oncogene, 21:532–40. De Sandre-Giovannoli A, Bernard R, Cau P, et al. 2003. Lamin A truncation in Hutchinson–Gilford progeria. Science, 300:2055. Du X, Shen J, Kugan N, et al. 2004. Telomere shortening exposes func- tions for the Werner and Bloom syndrome genes in mice. Mol Cell Biol, 24:8437–46. Epstein CJ, Martin GM, Schultz AL, et al. 1966. Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine, 45:177–221. Epstein J, Williams JR, and Little JB. 1973. Deﬁcient DNA repair in human progeroid cells. Proc Natl Acad Sci U S A, 70:977–81. Eriksson, M, Brown WT, Gordon LB, et al. 2003. Recurrent de novo point mutations in lamin a cause Hutchinson-Gilford progeria syndrome. Nature, 423:293–8. Fairall L, Chapman L, Moss H, et al. 2001. Structure of the TRFH dimer- ization domain of the human telomeric proteins TRF1 and TRF2. Mol Cell, 8:351–61. Fong LG, Ng JK, Lammerding J, et al. 2006. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest, 116:743–52. Fossel M. 2003. The progerias. J Antiaging Med, 6:123–38. 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. Fukuchi K, Katsuya T, Sugimoto K, et al. 2004. LMNA mutation in a 45 year old Japanese subject with Hutchinson-Gilford progeria syndrome. J Med Genet, 41:e67. Gilford H. 1904. Ateleiosis and progeria: continous youth and premature old age. Br Med J, 914–8. Glynn MW, Glover TW. 2005. Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition. Hum Mol Genet, 14:2959–69. Goldman RD, Gruenbaum Y, Moir RD, et al. 2002. Nuclear lamins: building blocks of nuclear architecture. Genes Dev, 16:533–47. Goldman RD, Shumaker DK, Erdos MR, et al. 2004. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci, USA, 101:8963–8. Goto M, Miller RW, Ishikawa Y, et al. 1996. Excess of rare cancers in Werner’s syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev, 5:239–46. Goto M. 1997. Hierarchical deterioration of body systems in Werner’s syndrome: Implications for normal ageing. Mech Ageing Dev, 98:239–54. Gray MD, Shen JC, Kamath-Loeb AS, et al. 1997. The Werner syndrome protein is a DNA helicase. Nat Genet, 17:100–3. Grifﬁth JD, Comeau L, Rosenﬁeld S, et al. 1999. Mammalian telomeres end in a large duplex loop. Cell, 97:503–14. 441