Navarro CL, Cau P, Levy N. 2006. Molecular bases of progeroid syndromes. Human Molecular Genetics, 15:R151–61. Ogburn CE, Oshima J, Poot M, et al. 1997. An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants. Hum Genet, 101:121–5. Ohsugi I, Tokutake Y, Suzuki N, et al. 2000. Telomere repeat DNA forms a large non-covalent complex with unique cohesive properties which is dissociated by Werner syndrome DNA helicase in the presence of replication protein A, Nucleic Acids Res, 28:3642–8. Opresko PL, Laine J-P, Brosh RM Jr, et al. 2001. Coordinate action of the helicase and 3’ to 5’ exonuclease of Werner syndrome protein, J Biol Chem, 276:44677–87. Opresko PL, von Kobbe C, Laine JP, et al. 2002. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicase. J Biol Chem, 277:41110–19. Opresko PL, Cheng WH, von Kobbe C, et al. 2003. Werner syndrome and the function of the Werner protein: what they can teach us about the molecular aging process. Carcinogenesis, 24:791–802. Opresko PL, Otterlei M, Graakjaer J, et al. 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. Orren DK, Machwe A, Karmakar P, et al. 2001. A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA. Nucleic Acids Res, 29:1926–34. Oshima J, Huang S, Pae C, et al. 2002. Lack of WRN results in extensive deletion at nonhomologous joining ends. Cancer Res, 62:547–51. Pichierri P, Rosselli F, Franchitto A. 2003. Werner’s syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replica- tion arrest and DNA damage induced during the S phase of the cell cycle. Oncogene, 22:1491–500. Poot M, Hoehn H, Runger TM, et al. 1992. Impaired S phase transit of Werner syndrome cells expressed in lymphoblastoid cells. Exp Cell Res, 202:267–73. Poot M, Yom JS, Whang SH, et al. 2001. Werner syndrome cells are sensi- tive to DNA cross-linking drugs. FASEB J, 15:1224–6. Poot M, Gollahon KA, Emond MJ, et al. 2002. Werner syndrome diploid ﬁbroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype. FASEB J, 16:757–8. Prince PR, Emond MJ, Monnat RJ Jr. 2001. Loss of Werner syndrome protein function promotes aberrant mitotic recombination. Genes Dev, 15:933–8. Prolla TA. 2005. Multiple roads to the aging phenotype: insights from the molecular dissection of progerias through DNA microarray analysis. Mech Ageing Dev, 126:461–5. Rodríguez-López AM, Jackson DA, Nehlin JO, et al. 2003. Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner’s syndrome, and an essential replication factor, PCNA. Mech Ageing Dev, 124:167–74. Saintigny Y, Makienko K, Swanson C, et al. 2002. Homologous recom- bination resolution defect in Werner syndrome. Mol Cell Biol, 22:6971–8. Sakamoto S, Nishikawa K, Heo SJ, et al. 2001. Werner helicase relocates into nuclear foci in response to DNA damaging agents and co-localizes with RPA and Rad51. Genes Cells, 6:421–30. Salk D, Bryant E, Hoehn H, et al. 1985. Growth characteristics of Werner syndrome cells in vitro. Adv Exp Med Biol, 190:305–11. Sanz MM, Proytcheva M, Ellis NA, et al. 2000. BLM, the Bloom’s syn- drome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins. Cytogenet Cell Genet, 91:217–23. Scafﬁdi P, Misteli T. 2005. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med, 11:440–5. Scafﬁdi P, Misteli T. 2006. Lamin A-dependent nuclear defects in human aging. Science, 312:1059–63. Clinical Interventions in Aging 2008:3(3) Werner’s and Hutchinson-Gilford progeria syndromes Schulz VP, Zakian V A, Ogburn CE, et al. 1996. Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells. Hum Genet, 97:750–4. Serrano M, Blasco MA. 2007. Cancer and ageing: convergent and divergent mechanisms. Nat Rev Mol Cell Biol, 8:715–22. Sharma S, Otterlei M, Sommers JA, et al. 2004. WRN helicase and FEN-1 form a complex upon replication arrest and together process branch- migrating DNA structures associated with the replication fork, Mol Biol Cell, 15:734–50. Sharma S, Sommers JA, Gary RK, et al. 2005. The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res, 33:6769–81. Shen JC, Gray MD, Oshima J, et al. 1998. Characterization of Werner syndrome protein DNA helicase activity: directionality, substrate dependence and stimulation by replication protein A. Nucleic Acids Res, 26:2879–85. Shen JC, Loeb LA. 2000. Werner syndrome exonuclease catalyzes structure- dependent degradation of DNA. Nucleic Acids Res, 28:3260–8. Shen JC, Lao Y, Kamath-Loeb A, et al. 2003. The N-terminal domain of the large subunit of human replication protein A binds to Werner syndrome protein and stimulates helicase activity, Mech Ageing Dev, 124:921–30. Shumaker DK, Dechat T, Kohlmaier A, et al. 2006. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A, 103:8703–8. Smogorzewska A, de Lange T. 2004. Regulation of telomerase by telomeric proteins. Annu Rev Biochem, 73:177–208. Sommers JA, Sharma S, Doherty KM, et al. 2005. p53 modulates RPA- dependent and RPA-independent WRN helicase activity. Cancer Res, 65:1223–33. Spann TP, Goldman AE,Wang C, et al. 2002. Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription. J Cell Biol, 156:603–8. Spillare EA, Robles AI, Wang XW, et al. 1999. p53-mediated apoptosis is attenuated in Werner syndrome cells. Genes Dev, 13:1355–60. Spillare EA, Wang XW, von Kobbe C, et al. 2006. Redundancy of DNA helicases in p53-mediated apoptosis. Oncogene, 25:2119–23. Sun QY, Schatten H. 2006. Role of NuMA in vertebrate cells: review of an intriguing multifunctional protein. Front Biosci, 11:1137–46. Suzuki N, Shimamoto A, Imamura O, et al. 1997. DNA helicase activity in Werner’s syndrome gene product synthesized in a baculovirus system. Nucleic Acids Res, 25:2973–8. Suzuki N, Shiratori M, Goto M, et al. 1999. Werner syndrome helicase contains a 5'→3' exonuclease activity that digests DNA and RNA strands in DNA/DNA and RNA/DNA duplexes dependent on unwind- ing. Nucleic Acids Res, 27:2361–8. Symonds H, Krall L, Remington L, et al. 1994. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell, 78:703–11. Szekely AM, Chen YH, Zhang C, et al. 2000. Werner protein recruits DNA polymerase δ to the nucleolus. Proc Natl Acad Sci, USA, 97:11365–70. Takai H, Smogorzewska A, de Lange T. 2003. DNA damage foci at dys- functional telomeres. Curr Biol, 13:1549–56. Takeuchi F, Hanaoka F, Goto M, et al. 1982. Altered frequency of initia- tion sites of DNA replication in Werner’s syndrome cells. Hum Genet, 60:365–8. Tauchi H, Kobayashi J, Morishima K, et al. 2002. Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature, 420:93–8. Toth JI, Yang SH, Qiao X, et al. 2005. Blocking protein farnesyltransferase improves nuclear shape in ﬁbroblasts from humans with progeroid syndromes. Proc Natl Acad Sci U S A, 102:12873–8. Tsai MY, Wang S, Heidinger JM, et al. 2006. A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science, 311:1887–93. Varela I, Cadinanos J, Pendas AM, et al. 2005. Accelerated ageing in mice deﬁcient in Zmpste24 protease is linked to p53 signalling activation. Nature, 437:564–8. 443