Ding and Shen Halaschek-Wiener J, Brooks-Wilson, A. 2007. Progeria of stem cells: stem cell exhaustion in hutchinson-gilford progeria syndrome. J Gerontol A Biol Sci Med Sci, 62:3–8. Hanaoka F, Yamada M, Takeuchi F, et al. 1985. Autoradiographic studies of DNA replication in Werner’s syndrome cells. Adv Exp Med Biol, 190:439–57. Harman D. 1956. Aging: a theory based on free radical and radiation chemistry. J Gerontol, 11:298–300. Harrigan JA, Opresko PL, von Kobbe C, et al. 2003. The Werner syndrome protein stimulates DNA polymerase beta strand displacement synthesis via its helicase activity. J Biol Chem, 278:22686–95. Hasty P, Campisi J, Hoeijmakers J, et al. 2003. Aging and genome mainte- nance: lessons from the mouse? Science, 299:1355–9. Hasty P, Vijg J. 2004. Accelerating aging by mouse reverse genetics: a rational approach to understand longevity. Aging Cell, 3:55–65. Haupt S, Berger M, Goldberg Z, et al. 2003. Apoptosis - the p53 network. J Cell Sci, 116:4077–85. Hennekam RC. 2006. Hutchinson-Gilford progeria syndrome: Review of the phenotype. Am J Med Genet A, 140:2603–24. Hickson ID. 2003. RecQ helicases: caretakers of the genome. Nat Rev Cancer, 3:169–78. Hofseth LJ, Hussain SP, Harris CC. 2004. p53: 25 years after its discovery. Trends Pharmacol Sci, 25:177–81. Horn HF, Vousden KH. 2007. Coping with stress: multiple ways to activate p53. Oncogene, 26:1306–16. Huang S, Li B, Gray MD, et al. 1998. The premature ageing syndrome protein, WRN, is a 3'→5' exonuclease. Nature Genet, 20:114–6. Huang S, Beresten S, Li B, et al. 2000. Characterization of the human and mouse WRN 3'→5' exonuclease. Nucleic Acids Res, 28:2396–405. Hutchinson J. 1886. Case of congenital absence of hair, with atrophic condi- tion of the skin and its apendages. Lancet, 923. Jeziorny L, McCurdy L, Michael K, et al. 2006. The Heli-CASE of the missing WRN gene. Eukaryon, 2:34–9. Kamath-Loeb AS, Johansson E, Burgers PM, et al. 2000. Functional interac- tion between the Werner syndrome protein and DNA polymerase delta. Proc Natl Acad Sci USA, 97:4603–8. Kamath-Loeb AS, Loeb LA, Johansson E, et al. 2001. Interactions between the Werner syndrome helicase and DNA polymerase d speciﬁcally facilitate copying of tetraplex and hairpin structures of the d(CGG)n trinucleotide repeat sequence. J Biol Chem, 276:16439–46. Karanjawala ZE, Lieber MR. 2004. DNA damage and aging. Mech Ageing Dev, 125:405–16. Karmakar P, Snowden CM, Ramsden DA, et al. 2002. Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus. Nucleic Acids Res, 30:3583–91. Kator K, Cristofalo V, Charpentier R, et al. 1985. Dysdifferentiative nature of aging: passage number dependency of globin gene expression in normal human diploid cells grown in tissue culture. Gerontology, 31:355–61. Kawabe Y, Seki M, Seki T, et al. 2000. Covalent modiﬁcation of the Werner’s syndrome gene product with the ubiquitin-related protein, SUMO-1. J Biol Chem, 275:20963–6. Kyng KJ, Bohr VA. 2005. Gene expression and DNA repair in progeroid syndromes and human aging. Ageing Res Rev, 4:579–602. Laine JP, Opresko PL, Indig FE, et al. 2003. Werner protein stimulates topoisomerase I DNA relaxation activity. Cancer Res, 63:7136–46. Lane D. 2004. Anthony Dipple Carcinogenesis Award. p53 from pathway to therapy. Carcinogenesis, 25:1077–81. Lebel M, Leder P. 1998. A deletion within the murine Werner syndrome heli- case induces sensitivity to inhibitors of topoisomerase and loss of cel- lular proliferative capacity. Proc Natl Acad Sci USA, 95:13097–102. Lebel M, Spillare EA, Harris CC, et al. 1999. The Werner syndrome gene product co-puriﬁes with the DNA replication complex and interacts with PCNA and topoisomerase I. J Biol Chem, 274:37795–9. Li B, Comai L. 2000. Functional interaction between Ku and the Werner syndrome protein in DNA end processing. J Biol Chem, 275:28349–52. 442 Li B, Comai L. 2001. Requirements for the nucleoytic processing of DNA ends by the Werner syndrome protein: Ku70/80 complex. J Biol Chem, 276:9896–902. Li B, Comai L. 2002. Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein. Nucleic Acids Res, 30:3653–61. Li B, Navarro S, Kasahara N, et al. 2004. Identiﬁcation and biochemi- cal characterization of a Werner’s syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1. J Biol Chem, 279:13659–67. Liu B, Wang J, Chan KM, et al. 2005. Genomic instability in laminopathy- based premature aging. Nat Med, 11:780–5. Liu Y, Rusinol A, Sinensky M, et al. 2006. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci, 119:4644–9. Liu Z, Macias MJ, Bottomley MJ, et al. 1999. The three-dimensional struc- ture of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Struct Fold Des, 7:1557–66. Lombard DB, Chua KF, Mostoslavsky R, et al. 2005. DNA repair, genome stability, and aging. Cell, 120:497–512. Ly DH, Lockhart DJ, Lerner RA, et al. 2000. Mitotic misregulation and human aging. Science, 287:2486–92. Machwe A, Xiao L, Orren DK. 2004. TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene, 23:149–56. Machwe A, Xiao L, Groden J, et al. 2005. RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange. J Biol Chem, 280:23397–407. Machwe A, Lozada EM, Xiao L, et al. 2006. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins.BMC Mol Biol, 7:1. Maier B, Gluba W, Bernier B, et al. 2004. Modulation of mammalian life span by the short isoform of p53. Genes Dev, 18:306–19. Mallampalli MP, Huyer G, Bendale P, et al. 2005. Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci, USA, 102:14416–21. Marciniak RA, Lombard DB, Johnson FB, et al. 1998. Nucleolar localiza- tion of the Werner syndrome protein in human cells. Proc Natl Acad Sci USA, 95:6887–92. Martin GM, Sprague CA, Epstein CJ. 1970. Replicative life-span of culti- vated human cells. Effects of donor’s age, tissue, and genotype. Lab Inves, 23:86–92. Martin GM. 1977. Cellular aging-clonal senescence. A review (Part I). Am J Pathol, 89:484–511. Martin GM. 1978. Genetic syndromes in man with potential relevance to the pathobiology of aging. Birth Defects Orig Artic Ser, 14:5–39. Martin GM. 1985. Genetics and aging: the Werner syndrome as a segmental progeroid syndrome. Adv Exp Med Biol, 190:161–70. Martin GM, Oshima J. 2000. Lessons from human progeroid syndromes. Nature, 408:263–6. Matsumoto T, Shimamoto A, Goto M, et al. 1997. Impaired nuclear localization of defective DNA helicases in Werner’s syndrome. Nat Genet, 16:335–6. McClintock B. 1941. The stability of broken ends of chromosomes in Zea mays. Genetics, 26:234–82. Merrill BJ, Holm C. 1998. The RAD52 recombinational repair pathway is essential in pol30 (PCNA) mutants that accumulate small single-stranded DNA fragments during DNA synthesis. Genetics, 148:611–24. Mohaghegh P, Karow JK, Brosh JR Jr, et al. 2001. The Bloom’s and Werner’s syndrome proteins are DNA structurespeciﬁc helicases. Nucleic Acids Res, 29:2843–49. Monnat RJ Jr, Saintigny Y. 2004. Werner syndrome protein-unwinding function to explain disease. Sci Aging Knowledge Environ, 2004:3. Müller S, Ledl A, Schmidt D. 2004. SUMO: a regulator of gene expression and genome integrity. Oncogene, 23:1998–2008. Nagao M, Sugimura T. 1976. Molecular biology of the carcinogen, 4- nitroquinoline 1-oxide. Adv Cancer Res, 23:131–69. Clinical Interventions in Aging 2008:3(3)