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DNA Damage and Lamins

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Cancer Biology and the Nuclear Envelope

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 773))

Abstract

The spatial and temporal organization of the genome has emerged as an additional level of regulation of nuclear functions. Structural proteins associated with the nuclear envelope play important roles in the organization of the genome. The nuclear lamina, a polymeric meshwork formed by lamins (A- and B-type) and lamin-associated proteins, is viewed as a scaffold for tethering chromatin and protein complexes regulating a variety of nuclear functions. Alterations in lamins function impact DNA transactions such as transcription, replication, and repair, as well as epigenetic modifications that change chromatin structure. These data, and the association of defective lamins with a whole variety of degenerative disorders, premature aging syndromes, and cancer, provide evidence for these proteins operating as caretakers of the genome. In this chapter, we summarize current knowledge about the function of lamins in the maintenance of genome integrity, with special emphasis on the role of A-type lamins in the maintenance of telomere homeostasis and mechanisms of DNA damage repair. These findings have begun to shed some light onto molecular mechanisms by which alterations in A-type lamins induce genomic instability and contribute to the pathophysiology of aging and aging-related diseases, especially cancer.

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Abbreviations

DDR:

DNA damage response

DSB:

Double-strand break

EDMD:

Emery–Dreifuss muscular dystrophy

FTI:

Farnesyltransferase inhibitor

HGPS:

Hutchinson–Gilford progeria syndrome

HR:

Homologous recombination

IR:

Ionizing radiation

IRIF:

Ionizing radiation-induced foci

LAD:

Lamin-associated domain

MADA:

Mandibuloacral dysplasia type A

MEF:

Mouse embryonic fibroblast

NER:

Nucleotide-excision repair

NHEJ:

Nonhomologous end-joining

ROS:

Reactive oxygen species

shRNA:

Short hairpin RNA

References

  1. Cremer T et al (2006) Chromosome territories—a functional nuclear landscape. Curr Opin Cell Biol 18(3):307–316

    PubMed  CAS  Google Scholar 

  2. Misteli T (2007) Beyond the sequence: cellular organization of genome function. Cell 128(4):787–800

    PubMed  CAS  Google Scholar 

  3. Schneider R, Grosschedl R (2007) Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev 21(23):3027–3043

    PubMed  CAS  Google Scholar 

  4. Broers JL et al (2006) Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev 86(3):967–1008

    PubMed  CAS  Google Scholar 

  5. Dechat T et al (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22(7):832–853

    PubMed Central  PubMed  CAS  Google Scholar 

  6. Taddei A et al (2004) The function of nuclear architecture: a genetic approach. Annu Rev Genet 38:305–345

    PubMed  CAS  Google Scholar 

  7. Bridger JM et al (1993) Internal lamin structures within G1 nuclei of human dermal fibroblasts. J Cell Sci 104(Pt 2):297–306

    PubMed  CAS  Google Scholar 

  8. Gerace L, Blum A, Blobel G (1978) Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution. J Cell Biol 79(2 Pt 1):546–566

    PubMed  CAS  Google Scholar 

  9. Goldman AE et al (1992) Pathway of incorporation of microinjected lamin A into the nuclear envelope. J Cell Biol 119(4):725–735

    PubMed  CAS  Google Scholar 

  10. Hozak P et al (1995) Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J Cell Sci 108(Pt 2):635–644

    PubMed  CAS  Google Scholar 

  11. McKeon FD, Kirschner MW, Caput D (1986) Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins. Nature 319(6053):463–468

    PubMed  CAS  Google Scholar 

  12. Guelen L et al (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453(7197):948–951

    PubMed  CAS  Google Scholar 

  13. Goldman RD et al (2002) Nuclear lamins: building blocks of nuclear architecture. Genes Dev 16(5):533–547

    PubMed  CAS  Google Scholar 

  14. Gruenbaum Y et al (2005) The nuclear lamina comes of age. Nat Rev Mol Cell Biol 6(1):21–31

    PubMed  CAS  Google Scholar 

  15. Stuurman N, Heins S, Aebi U (1998) Nuclear lamins: their structure, assembly, and interactions. J Struct Biol 122(1–2):42–66

    PubMed  CAS  Google Scholar 

  16. Lin F, Worman HJ (1993) Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. J Biol Chem 268(22):16321–16326

    PubMed  CAS  Google Scholar 

  17. Beck LA, Hosick TJ, Sinensky M (1990) Isoprenylation is required for the processing of the lamin A precursor. J Cell Biol 110(5):1489–1499

    PubMed  CAS  Google Scholar 

  18. Bergo MO et al (2002) Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc Natl Acad Sci U S A 99(20):13049–13054

    PubMed Central  PubMed  CAS  Google Scholar 

  19. Corrigan DP et al (2005) Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24. Biochem J 387(Pt 1):129–138

    PubMed Central  PubMed  CAS  Google Scholar 

  20. Pendas AM et al (2002) Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat Genet 31(1):94–99

    PubMed  CAS  Google Scholar 

  21. Schirmer EC, Foisner R (2007) Proteins that associate with lamins: many faces, many functions. Exp Cell Res 313(10):2167–2179

    PubMed  CAS  Google Scholar 

  22. Zastrow MS, Vlcek S, Wilson KL (2004) Proteins that bind A-type lamins: integrating isolated clues. J Cell Sci 117(Pt 7):979–987

    PubMed  CAS  Google Scholar 

  23. Capell BC, Collins FS (2006) Human laminopathies: nuclei gone genetically awry. Nat Rev Genet 7(12):940–952

    PubMed  CAS  Google Scholar 

  24. Prokocimer M et al (2009) Nuclear lamins: key regulators of nuclear structure and activities. J Cell Mol Med 13(6):1059–1085

    PubMed  CAS  Google Scholar 

  25. De Sandre-Giovannoli A et al (2003) Lamin a truncation in Hutchinson-Gilford progeria. Science 300(5628):2055

    PubMed  Google Scholar 

  26. Eriksson M et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423(6937):293–298

    PubMed  CAS  Google Scholar 

  27. Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140(23):2603–2624

    PubMed  Google Scholar 

  28. Varela I et al (2005) Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437(7058):564–568

    PubMed  CAS  Google Scholar 

  29. McClintock D et al (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2(12):e1269

    PubMed Central  PubMed  Google Scholar 

  30. Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312(5776):1059–1063

    PubMed Central  PubMed  CAS  Google Scholar 

  31. Agrelo R et al (2005) Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B-cell lymphoma. J Clin Oncol 23(17):3940–3947

    PubMed  CAS  Google Scholar 

  32. Broers JL et al (1993) Nuclear A-type lamins are differentially expressed in human lung cancer subtypes. Am J Pathol 143(1):211–220

    PubMed Central  PubMed  CAS  Google Scholar 

  33. Prokocimer M, Margalit A, Gruenbaum Y (2006) The nuclear lamina and its proposed roles in tumorigenesis: projection on the hematologic malignancies and future targeted therapy. J Struct Biol 155(2):351–360

    PubMed  CAS  Google Scholar 

  34. Willis ND et al (2008) Lamin A/C is a risk biomarker in colorectal cancer. PLoS One 3(8):e2988

    PubMed Central  PubMed  Google Scholar 

  35. Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362(6422):709–715

    PubMed  CAS  Google Scholar 

  36. Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411(6835):366–374

    PubMed  CAS  Google Scholar 

  37. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078

    PubMed Central  PubMed  CAS  Google Scholar 

  38. Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361(15):1475–1485

    PubMed  CAS  Google Scholar 

  39. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    PubMed  CAS  Google Scholar 

  40. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27(3):247–254

    PubMed  CAS  Google Scholar 

  41. Zhou BB, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408(6811):433–439

    PubMed  CAS  Google Scholar 

  42. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204

    PubMed Central  PubMed  CAS  Google Scholar 

  43. Hartlerode AJ, Scully R (2009) Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J 423(2):157–168

    PubMed Central  PubMed  CAS  Google Scholar 

  44. Mao Z et al (2008) Comparison of nonhomologous end joining and homologous recombination in human cells. DNA Repair (Amst) 7(10):1765–1771

    CAS  Google Scholar 

  45. Wyman C, Kanaar R (2006) DNA double-strand break repair: all’s well that ends well. Annu Rev Genet 40:363–383

    PubMed  CAS  Google Scholar 

  46. Shibata A et al (2011) Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J 30(6):1079–1092

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304(5667):93–96

    PubMed  CAS  Google Scholar 

  48. Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308(5721):551–554

    PubMed  CAS  Google Scholar 

  49. Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421(6922):499–506

    PubMed  CAS  Google Scholar 

  50. Khanna KK et al (2001) ATM, a central controller of cellular responses to DNA damage. Cell Death Differ 8(11):1052–1065

    PubMed  CAS  Google Scholar 

  51. Burma S et al (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276(45):42462–42467

    PubMed  CAS  Google Scholar 

  52. Fernandez-Capetillo O et al (2002) DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol 4(12):993–997

    PubMed  CAS  Google Scholar 

  53. Stewart GS et al (2003) MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421(6926):961–966

    PubMed  CAS  Google Scholar 

  54. Kolas NK et al (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318(5856):1637–1640

    PubMed Central  PubMed  CAS  Google Scholar 

  55. Mailand N et al (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131(5):887–900

    PubMed  CAS  Google Scholar 

  56. Doil C et al (2009) RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136(3):435–446

    PubMed  CAS  Google Scholar 

  57. Galanty Y et al (2009) Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462(7275):935–939

    PubMed Central  PubMed  CAS  Google Scholar 

  58. Morris JR et al (2009) The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature 462(7275):886–890

    PubMed  CAS  Google Scholar 

  59. Wang B et al (2002) 53BP1, a mediator of the DNA damage checkpoint. Science 298(5597):1435–1438

    PubMed  CAS  Google Scholar 

  60. Scully R et al (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88(2):265–275

    PubMed  CAS  Google Scholar 

  61. Liu B et al (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780–785

    PubMed  CAS  Google Scholar 

  62. Richards SA et al (2011) The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Hum Mol Genet 20(20):3997–4004

    PubMed  CAS  Google Scholar 

  63. di Masi A et al (2008) The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation. Cell Cycle 7(13):2030–2037

    PubMed  Google Scholar 

  64. Liu Y et al (2008) Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB J 22(2):603–611

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Liu GH et al (2011) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472(7342):221–225

    PubMed Central  PubMed  CAS  Google Scholar 

  66. Pegoraro G et al (2009) Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol 11(10):1261–1267

    PubMed Central  PubMed  CAS  Google Scholar 

  67. Krishnan V et al (2011) Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci U S A 108(30):12325–12330

    PubMed Central  PubMed  CAS  Google Scholar 

  68. de Lange T (2002) Protection of mammalian telomeres. Oncogene 21(4):532–540

    PubMed  Google Scholar 

  69. Smogorzewska A et al (2002) DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr Biol 12(19):1635–1644

    PubMed  CAS  Google Scholar 

  70. Raz V et al (2008) The nuclear lamina promotes telomere aggregation and centromere peripheral localization during senescence of human mesenchymal stem cells. J Cell Sci 121(Pt 24):4018–4028

    PubMed  CAS  Google Scholar 

  71. Shoeman RL et al (1988) The binding in vitro of the intermediate filament protein vimentin to synthetic oligonucleotides containing telomere sequences. J Biol Chem 263(35): 18744–18749

    PubMed  CAS  Google Scholar 

  72. Gonzalez-Suarez I et al (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28(16):2414–2427

    PubMed Central  PubMed  CAS  Google Scholar 

  73. De Vos WH et al (2010) Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins. Biochim Biophys Acta 1800(4):448–458

    PubMed  Google Scholar 

  74. Huang S et al (2008) Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. Exp Cell Res 314(1):82–91

    PubMed Central  PubMed  CAS  Google Scholar 

  75. Allsopp RC et al (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A 89(21):10114–10118

    PubMed Central  PubMed  CAS  Google Scholar 

  76. Decker ML et al (2009) Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev 130(6):377–383

    PubMed  CAS  Google Scholar 

  77. Kudlow BA et al (2008) Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53. Mol Biol Cell 19(12): 5238–5248

    PubMed Central  PubMed  CAS  Google Scholar 

  78. Redwood AB et al (2011) A dual role for A-type lamins in DNA double-strand break repair. Cell Cycle 10(15):2549–2560

    PubMed Central  PubMed  CAS  Google Scholar 

  79. Dimitrova N et al (2008) 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature 456(7221):524–528

    PubMed Central  PubMed  CAS  Google Scholar 

  80. Jahn D et al (2012) A truncated lamin A in the Lmna-/- mouse line: implications for the understanding of laminopathies. Nucleus 3(5):463–474

    PubMed Central  PubMed  Google Scholar 

  81. Sullivan T et al (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147(5):913–920

    PubMed Central  PubMed  CAS  Google Scholar 

  82. Difilippantonio S et al (2008) 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature 456(7221):529–533

    PubMed Central  PubMed  CAS  Google Scholar 

  83. Manis JP et al (2004) 53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination. Nat Immunol 5(5):481–487

    PubMed  CAS  Google Scholar 

  84. Ward IM et al (2004) 53BP1 is required for class switch recombination. J Cell Biol 165(4):459–464

    PubMed Central  PubMed  CAS  Google Scholar 

  85. Bothmer A et al (2010) 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination. J Exp Med 207(4):855–865

    PubMed Central  PubMed  CAS  Google Scholar 

  86. Bunting SF et al (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141(2):243–254

    PubMed Central  PubMed  CAS  Google Scholar 

  87. Olive PL, Banath JP, Durand RE (1990) Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the “comet” assay. Radiat Res 122(1):86–94

    PubMed  CAS  Google Scholar 

  88. Iliakis G et al (2004) Mechanisms of DNA double strand break repair and chromosome aberration formation. Cytogenet Genome Res 104(1–4):14–20

    PubMed  CAS  Google Scholar 

  89. Gonzalez-Suarez I et al (2011) A new pathway that regulates 53BP1 stability implicates Cathepsin L and vitamin D in DNA repair. EMBO J 30(16):3383–3396

    PubMed Central  PubMed  CAS  Google Scholar 

  90. Katunuma N (1989) Mechanisms and regulation of lysosomal proteolysis. Revis Biol Celular 20:35–61

    PubMed  CAS  Google Scholar 

  91. Goulet B et al (2004) A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Mol Cell 14(2):207–219

    PubMed  CAS  Google Scholar 

  92. Reiser J, Adair B, Reinheckel T (2010) Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 120(10):3421–3431

    PubMed Central  PubMed  CAS  Google Scholar 

  93. Gocheva V, Joyce JA (2007) Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 6(1):60–64

    PubMed  CAS  Google Scholar 

  94. Jedeszko C, Sloane BF (2004) Cysteine cathepsins in human cancer. Biol Chem 385(11):1017–1027

    PubMed  CAS  Google Scholar 

  95. Miyamoto K et al (2011) Cathepsin L is highly expressed in gastrointestinal stromal tumors. Int J Oncol 39(5):1109–1115

    PubMed  CAS  Google Scholar 

  96. Grotsky DA et al (2013) BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells. J Cell Biol 200(2):187–202

    PubMed Central  PubMed  CAS  Google Scholar 

  97. Bouwman P et al (2010) 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 17(6):688–695

    PubMed Central  PubMed  CAS  Google Scholar 

  98. Bindra RS, Glazer PM (2007) Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia. Oncogene 26(14):2048–2057

    PubMed  CAS  Google Scholar 

  99. Hegan DC et al (2010) Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proc Natl Acad Sci U S A 107(5):2201–2206

    PubMed Central  PubMed  CAS  Google Scholar 

  100. Johnson BR et al (2004) A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci U S A 101(26):9677–9682

    PubMed Central  PubMed  CAS  Google Scholar 

  101. Nitta RT, Smith CL, Kennedy BK (2007) Evidence that proteasome-dependent degradation of the retinoblastoma protein in cells lacking A-type lamins occurs independently of gankyrin and MDM2. PLoS One 2(9):e963

    PubMed Central  PubMed  Google Scholar 

  102. Fong LG et al (2006) Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 116(3):743–752

    PubMed Central  PubMed  CAS  Google Scholar 

  103. Varela I et al (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 14(7):767–772

    PubMed  CAS  Google Scholar 

  104. Osorio FG et al (2009) Accelerated ageing: from mechanism to therapy through animal models. Transgenic Res 18(1):7–15

    PubMed  CAS  Google Scholar 

  105. 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(20):2959–2969

    PubMed  CAS  Google Scholar 

  106. Toth JI et al (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc Natl Acad Sci U S A 102(36): 12873–12878

    PubMed Central  PubMed  CAS  Google Scholar 

  107. Yang SH et al (2005) Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc Natl Acad Sci U S A 102(29):10291–10296

    PubMed Central  PubMed  CAS  Google Scholar 

  108. Fong LG et al (2006) A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311(5767):1621–1623

    PubMed  CAS  Google Scholar 

  109. Gordon LB et al (2012) Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 109(41):16666–16671

    PubMed Central  PubMed  CAS  Google Scholar 

  110. Alvarez-Diaz S et al (2009) Cystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells. J Clin Invest 119(8):2343–2358

    PubMed  CAS  Google Scholar 

  111. Cao K et al (2011) Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci Transl Med 3(89):89ra58

    PubMed  CAS  Google Scholar 

  112. Sieprath T, Darwiche R, De Vos WH (2012) Lamins as mediators of oxidative stress. Biochem Biophys Res Commun 421(4):635–639

    PubMed  CAS  Google Scholar 

  113. Pekovic V et al (2011) Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation. Aging Cell 10(6):1067–1079

    PubMed  CAS  Google Scholar 

  114. Lattanzi G et al (2012) Nuclear damages and oxidative stress: new perspectives for laminopathies. Eur J Histochem 56(4):e45

    PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, 1100 S Grand Ave, St. Louis, MO, 63104, USA

    Susana Gonzalo

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  1. Susana Gonzalo
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Correspondence to Susana Gonzalo .

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Editors and Affiliations

  1. University of Edinburgh Wellcome Trust Centre for Cell Biology, Edinburgh, United Kingdom

    Eric C. Schirmer

  2. University of Edinburgh Wellcome Trust Centre for Cell Biology, Edinburgh, United Kingdom

    Jose I. de las Heras

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Gonzalo, S. (2014). DNA Damage and Lamins. In: Schirmer, E., de las Heras, J. (eds) Cancer Biology and the Nuclear Envelope. Advances in Experimental Medicine and Biology, vol 773. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8032-8_17

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