1932

Abstract

DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021115-105127
2016-02-10
2024-05-05
Loading full text...

Full text loading...

/deliver/fulltext/physiol/78/1/annurev-physiol-021115-105127.html?itemId=/content/journals/10.1146/annurev-physiol-021115-105127&mimeType=html&fmt=ahah

Literature Cited

  1. Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. 1.  2002. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 106:927–32 [Google Scholar]
  2. Matthews C, Gorenne I, Scott S, Figg N, Kirkpatrick P. 2.  et al. 2006. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res. 99:156–64 [Google Scholar]
  3. Mahmoudi M, Gorenne I, Mercer J, Figg N, Littlewood T, Bennett M. 3.  2008. Statins use a novel Nijmegen breakage syndrome-1–dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circ. Res. 103:717–25 [Google Scholar]
  4. Bennett MR, Evan GI, Schwartz SM. 4.  1995. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J. Clin. Investig. 95:2266–74 [Google Scholar]
  5. Tabas I. 5.  2005. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler. Thromb. Vasc. Biol. 25:2255–64 [Google Scholar]
  6. Gray KL, Kumar SV, Figg N, Harrison J, Baker L. 6.  et al. 2014. Effects of DNA damage in smooth muscle cells in atherosclerosis. Circ. Res. 116:816–26 [Google Scholar]
  7. Botto N, Rizza A, Colombo MG, Mazzone AM, Manfredi S. 7.  et al. 2001. Evidence for DNA damage in patients with coronary artery disease. Mutat. Res. 493:23–30 [Google Scholar]
  8. Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. 8.  2001. Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ. Res. 88:733–39 [Google Scholar]
  9. Cafueri G, Parodi F, Pistorio A, Bertolotto M, Ventura F. 9.  et al. 2012. Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition. PLOS ONE 7:e35312 [Google Scholar]
  10. Acilan C, Serhatli M, Kacar O, Adiguzel Z, Tuncer A. 10.  et al. 2012. Smooth muscle cells isolated from thoracic aortic aneurysms exhibit increased genomic damage, but similar tendency for apoptosis. DNA Cell Biol. 31:1523–34 [Google Scholar]
  11. Sharma NK, Lebedeva M, Thomas T, Kovalenko OA, Stumpf JD. 11.  et al. 2014. Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia. DNA Repair 13:22–31 [Google Scholar]
  12. Schneider JG, Finck BN, Ren J, Standley KN, Takagi M. 12.  et al. 2006. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab. 4:377–89 [Google Scholar]
  13. Mercer JR, Cheng KK, Figg N, Gorenne I, Mahmoudi M. 13.  et al. 2010. DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome. Circ. Res. 107:1021–31 [Google Scholar]
  14. Mercer JR, Yu E, Figg N, Cheng KK, Prime TA. 14.  et al. 2012. The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/−/ApoE−/− mice. Free Radic. Biol. Med. 52:841–49 [Google Scholar]
  15. Crabbe L, Verdun RE, Haggblom CI, Karlseder J. 15.  2004. Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306:1951–53 [Google Scholar]
  16. Burtner CR, Kennedy BK. 16.  2010. Progeria syndromes and ageing: What is the connection?. Nat. Rev. Mol. Cell Biol. 11:567–78 [Google Scholar]
  17. Olive M, Harten I, Mitchell R, Beers JK, Djabali K. 17.  et al. 2010. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler. Thromb. Vasc. Biol. 30:2301–9 [Google Scholar]
  18. Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y. 18.  2006. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J. Cell Sci. 119:4644–49 [Google Scholar]
  19. Scaffidi P, Misteli T. 19.  2006. Lamin A–dependent nuclear defects in human aging. Science 312:1059–63 [Google Scholar]
  20. Ragnauth CD, Warren DT, Liu Y, McNair R, Tajsic T. 20.  et al. 2010. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 121:2200–10 [Google Scholar]
  21. Lindahl T, Nyberg B. 21.  1972. Rate of depurination of native deoxyribonucleic acid. Biochemistry 11:3610–18 [Google Scholar]
  22. Caldecott KW. 22.  2008. Single-strand break repair and genetic disease. Nat. Rev. Genet. 9:619–31 [Google Scholar]
  23. Hartlerode AJ, Scully R. 23.  2009. Mechanisms of double-strand break repair in somatic mammalian cells. Biochem. J. 423:157–68 [Google Scholar]
  24. Chapman JR, Taylor MR, Boulton SJ. 24.  2012. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47:497–510 [Google Scholar]
  25. Pardo B, Gomez-Gonzalez B, Aguilera A. 25.  2009. DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship. Cell. Mol. Life Sci. 66:1039–56 [Google Scholar]
  26. Rupnik A, Grenon M, Lowndes N. 26.  2008. The MRN complex. Curr. Biol. 18:R455–57 [Google Scholar]
  27. Botto N, Berti S, Manfredi S, Al-Jabri A, Federici C. 27.  et al. 2005. Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease. Mutat. Res. 570:81–88 [Google Scholar]
  28. Yu E, Calvert PA, Mercer JR, Harrison J, Baker L. 28.  et al. 2013. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation 128:702–12 [Google Scholar]
  29. Ballinger SW, Patterson C, Knight-Lozano CA, Burow DL, Conklin CA. 29.  et al. 2002. Mitochondrial integrity and function in atherogenesis. Circulation 106:544–49 [Google Scholar]
  30. Aubert G, Lansdorp PM. 30.  2008. Telomeres and aging. Physiol. Rev. 88:557–79 [Google Scholar]
  31. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A. 31.  et al. 1999. Mammalian telomeres end in a large duplex loop. Cell 97:503–14 [Google Scholar]
  32. van Steensel B, Smogorzewska A, de Lange T. 32.  1998. TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–13 [Google Scholar]
  33. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. 33.  1999. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283:1321–25 [Google Scholar]
  34. Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y. 34.  et al. 2006. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126:49–62 [Google Scholar]
  35. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P. 35.  et al. 2003. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426:194–98 [Google Scholar]
  36. Ogami M, Ikura Y, Ohsawa M, Matsuo T, Kayo S. 36.  et al. 2004. Telomere shortening in human coronary artery diseases. Arterioscler. Thromb. Vasc. Biol. 24:546–50 [Google Scholar]
  37. Carracedo J, Merino A, Briceno C, Soriano S, Buendia P. 37.  et al. Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells. FASEB J. 25:1314–22 [Google Scholar]
  38. Brouilette S, Singh RK, Thompson JR, Goodall AH, Samani NJ. 38.  2003. White cell telomere length and risk of premature myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 23:842–46 [Google Scholar]
  39. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I. 39.  et al. 2007. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 369:107–14 [Google Scholar]
  40. Panayiotou AG, Nicolaides AN, Griffin M, Tyllis T, Georgiou N. 40.  et al. 2010. Leukocyte telomere length is associated with measures of subclinical atherosclerosis. Atherosclerosis 211:176–81 [Google Scholar]
  41. Willeit P, Willeit J, Brandstatter A, Ehrlenbach S, Mayr A. 41.  et al. 2010. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler. Thromb. Vasc. Biol. 30:1649–56 [Google Scholar]
  42. Chang E, Harley CB. 42.  1995. Telomere length and replicative aging in human vascular tissues. PNAS 92:11190–94 [Google Scholar]
  43. Nzietchueng R, Elfarra M, Nloga J, Labat C, Carteaux JP. 43.  et al. 2011. Telomere length in vascular tissues from patients with atherosclerotic disease. J. Nutr. Health Aging 15:153–56 [Google Scholar]
  44. Dandona P, Aljada A. 44.  2002. A rational approach to pathogenesis and treatment of type 2 diabetes mellitus, insulin resistance, inflammation, and atherosclerosis. Am. J. Cardiol. 90:G27–33 [Google Scholar]
  45. Tatarkova Z, Kuka S, Racay P, Lehotsky J, Dobrota D. 45.  et al. 2011. Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol. Res. 60:281–89 [Google Scholar]
  46. Sampson MJ, Astley S, Richardson T, Willis G, Davies IR. 46.  et al. 2001. Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of α-tocopherol supplementation. Clin. Sci. 101:235–41 [Google Scholar]
  47. Sampson MJ, Winterbone MS, Hughes JC, Dozio N, Hughes DA. 47.  2006. Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care 29:283–89 [Google Scholar]
  48. Vendrov AE, Hakim ZS, Madamanchi NR, Rojas M, Madamanchi C, Runge MS. 48.  2007. Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells. Arterioscler. Thromb. Vasc. Biol. 27:2714–21 [Google Scholar]
  49. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL. 49.  et al. 1979. Risk factors for doxorubicin-induced congestive heart failure. Ann. Intern. Med. 91:710–17 [Google Scholar]
  50. Velez JM, Miriyala S, Nithipongvanitch R, Noel T, Plabplueng CD. 50.  et al. 2011. p53 regulates oxidative stress–mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury. PLOS ONE 6:e18005 [Google Scholar]
  51. van den Belt–Dusebout AW, Nuver J, de Wit R, Gietema JA, ten Bokkel Huinink WW. 51.  et al. 2006. Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J. Clin. Oncol. 24:467–75 [Google Scholar]
  52. Van Der Meeren A, Squiban C, Gourmelon P, Lafont H, Gaugler MH. 52.  1999. Differential regulation by IL-4 and IL-10 of radiation-induced IL-6 and IL-8 production and ICAM-1 expression by human endothelial cells. Cytokine 11:831–38 [Google Scholar]
  53. Stewart FA, Heeneman S, Te Poele J, Kruse J, Russell NS. 53.  et al. 2006. Ionizing radiation accelerates the development of atherosclerotic lesions in ApoE−/− mice and predisposes to an inflammatory plaque phenotype prone to hemorrhage. Am. J. Pathol. 168:649–58 [Google Scholar]
  54. Kastan MB, Bartek J. 54.  2004. Cell-cycle checkpoints and cancer. Nature 432:316–23 [Google Scholar]
  55. Jackson SP. 55.  2002. Sensing and repairing DNA double-strand breaks. Carcinogenesis 23:687–96 [Google Scholar]
  56. Jackson SP, Bartek J. 56.  2009. The DNA-damage response in human biology and disease. Nature 461:1071–78 [Google Scholar]
  57. Gray K, Bennett M. 57.  2011. Role of DNA damage in atherosclerosis—bystander or participant?. Biochem. Pharmacol. 82:693–700 [Google Scholar]
  58. Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y. 58.  2003. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 22:5612–21 [Google Scholar]
  59. Lamarche BJ, Orazio NI, Weitzman MD. 59.  2010. The MRN complex in double-strand break repair and telomere maintenance. FEBS Lett. 584:3682–95 [Google Scholar]
  60. Polo SE, Jackson SP. 60.  2011. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25:409–33 [Google Scholar]
  61. Desai-Mehta A, Cerosaletti KM, Concannon P. 61.  2001. Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization. Mol. Cell. Biol. 21:2184–91 [Google Scholar]
  62. Paull TT, Gellert M. 62.  1998. The 3′ to 5′ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol. Cell 1:969–79 [Google Scholar]
  63. Williams RS, Moncalian G, Williams JS, Yamada Y, Limbo O. 63.  et al. 2008. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 135:97–109 [Google Scholar]
  64. de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C. 64.  2001. Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol. Cell 8:1129–35 [Google Scholar]
  65. Yun MH, Hiom K. 65.  2009. CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Nature 459:460–63 [Google Scholar]
  66. Walker JR, Corpina RA, Goldberg J. 66.  2001. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412:607–14 [Google Scholar]
  67. Rivera-Calzada A, Spagnolo L, Pearl LH, Llorca O. 67.  2007. Structural model of full-length human Ku70–Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Rep. 8:56–62 [Google Scholar]
  68. Ochi T, Sibanda BL, Wu Q, Chirgadze DY, Bolanos-Garcia VM, Blundell TL. 68.  2010. Structural biology of DNA repair: spatial organisation of the multicomponent complexes of nonhomologous end joining. J. Nucleic Acids 2010:621695 [Google Scholar]
  69. Dynan WS, Yoo S. 69.  1998. Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids. Nucleic Acids Res. 26:1551–59 [Google Scholar]
  70. Takai H, Smogorzewska A, de Lange T. 70.  2003. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13:1549–56 [Google Scholar]
  71. Smogorzewska A, Karlseder J, Holtgreve-Grez H, Jauch A, de Lange T. 71.  2002. DNA ligase IV–dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr. Biol. 12:1635–44 [Google Scholar]
  72. Bae NS, Baumann P. 72.  2007. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol. Cell 26:323–34 [Google Scholar]
  73. Yan S, Sorrell M, Berman Z. 73.  2014. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cell. Mol. Life Sci. 71:3951–67 [Google Scholar]
  74. Bakkenist CJ, Kastan MB. 74.  2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506 [Google Scholar]
  75. Kastan MB. 75.  2008. DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture.. Mol. Cancer Res. 6:517–24 [Google Scholar]
  76. Spycher C, Miller ES, Townsend K, Pavic L, Morrice NA. 76.  et al. 2008. Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J. Cell Biol. 181:227–40 [Google Scholar]
  77. Mattiroli F, Vissers JH, van Dijk WJ, Ikpa P, Citterio E. 77.  et al. 2012. RNF168 ubiquitinates K13–15 on H2A/H2AX to drive DNA damage signaling. Cell 150:1182–95 [Google Scholar]
  78. Bartek J, Lukas J. 78.  2003. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–29 [Google Scholar]
  79. Falck J, Mailand N, Syljuasen RG, Bartek J, Lukas J. 79.  2001. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410:842–47 [Google Scholar]
  80. Iliakis G, Wang Y, Guan J, Wang H. 80.  2003. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene 22:5834–47 [Google Scholar]
  81. Abraham RT. 81.  2001. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 15:2177–96 [Google Scholar]
  82. Freedman DA, Wu L, Levine AJ. 82.  1999. Functions of the MDM2 oncoprotein. Cell. Mol. Life Sci. 55:96–107 [Google Scholar]
  83. Dimri GP, Nakanishi M, Desprez PY, Smith JR, Campisi J. 83.  1996. Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein. Mol. Cell. Biol. 16:2987–97 [Google Scholar]
  84. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R. 84.  et al. 1993. WAF1, a potential mediator of p53 tumor suppression. Cell 75:817–25 [Google Scholar]
  85. Lukas J, Lukas C, Bartek J. 85.  2004. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair 3:997–1007 [Google Scholar]
  86. Krokan HE, Standal R, Slupphaug G. 86.  1997. DNA glycosylases in the base excision repair of DNA. Biochem. J. 325:1–16 [Google Scholar]
  87. Kim YJ, Wilson DM. 87.  2012. Overview of base excision repair biochemistry. Curr. Mol. Pharmacol. 5:3–13 [Google Scholar]
  88. Kasai H, Chung MH, Jones DS, Inoue H, Ishikawa H. 88.  et al. 1991. 8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical–involved mutagenesis/carcinogenesis. J. Toxicol. Sci. 16:95–105 [Google Scholar]
  89. Candeias LP, Steenken S. 89.  2000. Reaction of HO with guanine derivatives in aqueous solution: formation of two different redox-active OH-adduct radicals and their unimolecular transformation reactions. Properties of G(-H). Chemistry 6:475–84 [Google Scholar]
  90. David SS, O'Shea VL, Kundu S. 90.  2007. Base-excision repair of oxidative DNA damage. Nature 447:941–50 [Google Scholar]
  91. Hegde ML, Hazra TK, Mitra S. 91.  2008. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res. 18:27–47 [Google Scholar]
  92. Fortini P, Parlanti E, Sidorkina OM, Laval J, Dogliotti E. 92.  1999. The type of DNA glycosylase determines the base excision repair pathway in mammalian cells. J. Biol. Chem. 274:15230–36 [Google Scholar]
  93. Cappelli E, Taylor R, Cevasco M, Abbondandolo A, Caldecott K, Frosina G. 93.  1997. Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. J. Biol. Chem. 272:23970–75 [Google Scholar]
  94. Caldecott KW. 94.  2007. Mammalian single-strand break repair: mechanisms and links with chromatin. DNA Repair 6:443–53 [Google Scholar]
  95. Skarpengland T, Laugsand LE, Janszky I, Luna L, Halvorsen B. 95.  et al. 2015. Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case-control study. The HUNT Study. DNA Repair 28:21–27 [Google Scholar]
  96. de Laat WL, Jaspers NG, Hoeijmakers JH. 96.  1999. Molecular mechanism of nucleotide excision repair. Genes Dev. 13:768–85 [Google Scholar]
  97. Kamileri I, Karakasilioti I, Garinis GA. 97.  2012. Nucleotide excision repair: new tricks with old bricks. Trends Genet. 28:566–73 [Google Scholar]
  98. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH. 98.  2014. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15:465–81 [Google Scholar]
  99. Durik M, Kavousi M, van der Pluijm I, Isaacs A, Cheng C. 99.  et al. 2012. Nucleotide excision DNA repair is associated with age-related vascular dysfunction. Circulation 126:468–78 [Google Scholar]
  100. Lieber MR. 100.  2008. The mechanism of human nonhomologous DNA end joining. J. Biol. Chem. 283:1–5 [Google Scholar]
  101. San Filippo J, Sung P, Klein H. 101.  2008. Mechanism of eukaryotic homologous recombination. Annu. Rev. Biochem. 77:229–57 [Google Scholar]
  102. Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A. 102.  2015. Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination. Nature 518:254–57 [Google Scholar]
  103. Davis AJ, Chen DJ. 103.  2013. DNA double strand break repair via non-homologous end-joining. Transl. Cancer Res. 2:130–43 [Google Scholar]
  104. Chen F, Peterson SR, Story MD, Chen DJ. 104.  1996. Disruption of DNA-PK in Ku80 mutant xrs-6 and the implications in DNA double-strand break repair. Mutat. Res. 362:9–19 [Google Scholar]
  105. Merkle D, Douglas P, Moorhead GB, Leonenko Z, Yu Y. 105.  et al. 2002. The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation. Biochemistry 41:12706–14 [Google Scholar]
  106. Cui X, Yu Y, Gupta S, Cho YM, Lees-Miller SP, Meek K. 106.  2005. Autophosphorylation of DNA-dependent protein kinase regulates DNA end processing and may also alter double-strand break repair pathway choice. Mol. Cell. Biol. 25:10842–52 [Google Scholar]
  107. Reddy YV, Ding Q, Lees-Miller SP, Meek K, Ramsden DA. 107.  2004. Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends. J. Biol. Chem. 279:39408–13 [Google Scholar]
  108. Feng L, Chen J. 108.  2012. The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. Nat. Struct. Mol. Biol. 19:201–6 [Google Scholar]
  109. Yu X, Chen J. 109.  2004. DNA damage–induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol. Cell. Biol. 24:9478–86 [Google Scholar]
  110. Chen L, Nievera CJ, Lee AY, Wu X. 110.  2008. Cell cycle–dependent complex formation of BRCA1·CtIP·MRN is important for DNA double-strand break repair. J. Biol. Chem. 283:7713–20 [Google Scholar]
  111. You Z, Bailis JM. 111.  2010. DNA damage and decisions: CtIP coordinates DNA repair and cell cycle checkpoints. Trends Cell Biol. 20:402–9 [Google Scholar]
  112. Escribano-Diaz C, Orthwein A, Fradet-Turcotte A, Xing M, Young JT. 112.  et al. 2013. A cell cycle–dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol. Cell 49:872–83 [Google Scholar]
  113. Chapman JR, Barral P, Vannier JB, Borel V, Steger M. 113.  et al. 2013. RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol. Cell 49:858–71 [Google Scholar]
  114. Zimmermann M, Lottersberger F, Buonomo SB, Sfeir A, de Lange T. 114.  2013. 53BP1 regulates DSB repair using Rif1 to control 5′ end resection. Science 339:700–4 [Google Scholar]
  115. Imaeda A, Aoki T, Kondo Y, Hori M, Ogata M. 115.  et al. 2001. Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis. Free Radic. Res. 34:33–44 [Google Scholar]
  116. Harangi M, Seres I, Varga Z, Emri G, Szilvassy Z. 116.  et al. 2004. Atorvastatin effect on high-density lipoprotein–associated paraoxonase activity and oxidative DNA damage. Eur. J. Clin. Pharmacol. 60:685–91 [Google Scholar]
  117. Shin MJ, Cho EY, Jang Y, Lee JH, Shim WH. 117.  et al. 2005. A beneficial effect of simvastatin on DNA damage in 242T allele of the NADPH oxidase p22phox in hypercholesterolemic patients. Clin. Chim. Acta 360:46–51 [Google Scholar]
  118. Di Leonardo A, Linke SP, Clarkin K, Wahl GM. 118.  1994. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 8:2540–51 [Google Scholar]
  119. Campisi J. 119.  2005. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–22 [Google Scholar]
  120. McKee JA, Banik SS, Boyer MJ, Hamad NM, Lawson JH. 120.  et al. 2003. Human arteries engineered in vitro. EMBO Rep. 4:633–38 [Google Scholar]
  121. Poch E, Carbonell P, Franco S, Diez-Juan A, Blasco MA, Andres V. 121.  2004. Short telomeres protect from diet-induced atherosclerosis in apolipoprotein E–null mice. FASEB J. 18:418–20 [Google Scholar]
  122. Herbert KE, Mistry Y, Hastings R, Poolman T, Niklason L, Williams B. 122.  2008. Angiotensin II–mediated oxidative DNA damage accelerates cellular senescence in cultured human vascular smooth muscle cells via telomere-dependent and independent pathways. Circ. Res. 102:201–8 [Google Scholar]
  123. Toussaint O, Medrano EE, von Zglinicki T. 123.  2000. Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp. Gerontol. 35:927–45 [Google Scholar]
  124. Olsson A, Manzl C, Strasser A, Villunger A. 124.  2007. How important are post-translational modifications in p53 for selectivity in target-gene transcription and tumour suppression?. Cell Death Differ. 14:1561–75 [Google Scholar]
  125. McIlwain DR, Berger T, Mak TW. 125.  2013. Caspase functions in cell death and disease. Cold Spring Harb. Perspect. Biol. 5:1–28 [Google Scholar]
  126. Bennett MR. 126.  2002. Apoptosis in the cardiovascular system. Heart 87:480–87 [Google Scholar]
  127. Saraste A, Pulkki K. 127.  2000. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc. Res. 45:528–37 [Google Scholar]
  128. Geng YJ, Libby P. 128.  1995. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1β-converting enzyme. Am. J. Pathol. 147:251–66 [Google Scholar]
  129. Isner JM, Kearney M, Bortman S, Passeri J. 129.  1995. Apoptosis in human atherosclerosis and restenosis. Circulation 91:2703–11 [Google Scholar]
  130. Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. 130.  1995. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am. J. Pathol. 147:267–77 [Google Scholar]
  131. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M. 131.  et al. 2006. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat. Med. 12:1075–80 [Google Scholar]
  132. Clarke MC, Littlewood TD, Figg N, Maguire JJ, Davenport AP. 132.  et al. 2008. Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration. Circ. Res. 102:1529–38 [Google Scholar]
  133. Passos JF, Nelson G, Wang C, Richter T, Simillion C. 133.  et al. 2010. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol. Syst. Biol. 6:347 [Google Scholar]
  134. van Deursen JM. 134.  2014. The role of senescent cells in ageing. Nature 509:439–46 [Google Scholar]
  135. Fyhrquist F, Saijonmaa O, Strandberg T. 135.  2013. The roles of senescence and telomere shortening in cardiovascular disease. Nat. Rev. Cardiol. 10:274–83 [Google Scholar]
  136. Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A. 136.  et al. 2008. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:1006–18 [Google Scholar]
  137. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P. 137.  et al. 2013. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15:978–90 [Google Scholar]
  138. Davalos AR, Coppe JP, Campisi J, Desprez PY. 138.  2010. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 29:273–83 [Google Scholar]
  139. Katsuda S, Kaji T. 139.  2003. Atherosclerosis and extracellular matrix. J. Atheroscler. Thromb. 10:267–74 [Google Scholar]
  140. Rodier F, Coppe JP, Patil CK, Hoeijmakers WA, Munoz DP. 140.  et al. 2009. Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11:973–79 [Google Scholar]
  141. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. 141.  2013. The hallmarks of aging. Cell 153:1194–217 [Google Scholar]
  142. Martínez P, Blasco MA. 142.  2011. Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat. Rev. Cancer 11:161–76 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021115-105127
Loading
/content/journals/10.1146/annurev-physiol-021115-105127
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error