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Telomeres, DNA Damage Response and Genomic Instability

Telomeres, histone code, and DNA damage response

Misri S. · Pandita S. · Kumar R. · Pandita T.K.

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Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (USA)

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Cytogenet Genome Res 122:297–307 (2008)

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Article / Publication Details

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Abstract of Telomeres, DNA Damage Response and Genomic Instability

Received: September 15, 2008
Published online: January 30, 2009
Issue release date: February 2009

Number of Print Pages: 11
Number of Figures: 3
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

Abstract

Genomic stability is maintained by telomeres, the end terminal structures that protect chromosomes from fusion or degradation. Shortening or loss of telomeric repeats or altered telomere chromatin structure is correlated with telomere dysfunction such as chromosome end-to-end associations that could lead to genomic instability and gene amplification. The structure at the end of telomeres is such that its DNA differs from DNA double strand breaks (DSBs) to avoid nonhomologous end-joining (NHEJ), which is accomplished by forming a unique higher order nucleoprotein structure. Telomeres are attached to the nuclear matrix and have a unique chromatin structure. Whether this special structure is maintained by specific chromatin changes is yet to be thoroughly investigated. Chromatin modifications implicated in transcriptional regulation are thought to be the result of a code on the histone proteins (histone code). This code, involving phosphorylation, acetylation, methylation, ubiquitylation, and sumoylation of histones, is believed to regulate chromatin accessibility either by disrupting chromatin contacts or by recruiting non-histone proteins to chromatin. The histone code in which distinct histone tail-protein interactions promote engagement may be the deciding factor for choosing specific DSB repair pathways. Recent evidence suggests that such mechanisms are involved in DNA damage detection and repair. Altered telomere chromatin structure has been linked to defective DNA damage response (DDR), and eukaryotic cells have evolved DDR mechanisms utilizing proficient DNA repair and cell cycle checkpoints in order to maintain genomic stability. Recent studies suggest that chromatin modifying factors play a critical role in the maintenance of genomic stability. This review will summarize the role of DNA damage repair proteins specifically ataxia-telangiectasia mutated (ATM) and its effectors and the telomere complex in maintaining genome stability.

© 2008 S. Karger AG, Basel


References

  1. Agarwal M, Pandita S, Hunt CR, Gupta A, Yue X, et al: Inhibition of telomerase activity enhances hyperthermia-mediated radiosensitization. Cancer Res 68:3370–3378 (2008).
  2. Andegeko Y, Moyal L, Mittelman L, Tsarfaty I, Shiloh Y, Rotman G: Nuclear retention of ATM at sites of DNA double strand breaks. J Biol Chem 276:38224–38230 (2001).
  3. Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR: HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453:682–686 (2008).
  4. Bailey SM, Meyne J, Chen DJ, Kurimasa A, Li GC, et al: DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc Natl Acad Sci USA 96:14899–14904 (1999).
  5. Bakkenist CJ, Kastan MB: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506 (2003).
  6. Bannister AJ, Schneider R, Kouzarides T: Histone methylation: dynamic or static? Cell 109:801–806 (2002).
  7. Baskaran R, Wood LD, Whitaker LL, Canman CE, Morgan SE, et al: Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 387:516–519 (1997).
  8. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, et al: Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127:1361–1373 (2006).
  9. Boulton SJ, Jackson SP: Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res 24:4639–4648 (1996).
  10. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, et al: Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665 (2005).
  11. Cary RB, Peterson SR, Wang J, Bear DG, Bradbury EM, Chen DJ: DNA looping by Ku and the DNA-dependent protein kinase. Proc Natl Acad Sci USA 94:4267–4272 (1997).
  12. Chan SW, Chang J, Prescott J, Blackburn EH: Altering telomere structure allows telomerase to act in yeast lacking ATM kinases. Curr Biol 11:1240–1250 (2001).
  13. Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B: 14-3-3σ is required to prevent mitotic catastrophe after DNA damage. Nature 401:616–620 (1999).
  14. Chen MJ, Lin YT, Lieberman HB, Chen G, Lee EY: ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation. J Biol Chem 276:16580–16586 (2001).
  15. Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J: Gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 20:801–809 (2005).
  16. Critchlow SE, Jackson SP: DNA end-joining: from yeast to man. Trends Biochem Sci 23:394–398 (1998).
  17. de Lange T: Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110 (2005).
  18. Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM: Structure and ligand of a histone acetyltransferase bromodomain. Nature 399:491–496 (1999).
  19. Dhar S, Squire JA, Hande MP, Wellinger RJ, Pandita TK: Inactivation of 14-3-3σ influences telomere behavior and ionizing radiation-induced chromosomal instability. Mol Cell Biol 20:7764–7772 (2000).
  20. Dynan WS, Yoo S: Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids. Nucleic Acids Res 26:1551–1559 (1998).
  21. Eissenberg JC, Elgin SC: The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev 10:204–210 (2000).
  22. Fernandez-Capetillo O, Nussenzweig A: Linking histone deacetylation with the repair of DNA breaks. Proc Natl Acad Sci USA 101:1427–1428 (2004).
  23. Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, et al: H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4:497–508 (2003).
  24. Fernandez-Capetillo O, Allis CD, Nussenzweig A: Phosphorylation of histone H2B at DNA double-strand breaks. J Exp Med 199:1671–1677 (2004).
  25. Fischle W, Wang Y, Allis CD: Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183 (2003).
  26. Galande S, Kohwi-Shigematsu T: Poly(ADP-ribose) polymerase and Ku autoantigen form a complex and synergistically bind to matrix attachment sequences. J Biol Chem 274:20521–20528 (1999).
  27. Gasser SM: A sense of the end. Science 288:1377–1379 (2000).
  28. Gately DP, Hittle JC, Chan GK, Yen TJ: Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity. Mol Biol Cell 9:2361–2374 (1998).
  29. Giffin W, Torrance H, Rodda DJ, Prefontaine GG, Pope L, Hache RJ: Sequence-specific DNA binding by Ku autoantigen and its effects on transcription. Nature 380:265–268 (1996).
  30. Gilley D, Tanaka H, Hande MP, Kurimasa A, Li GC, et al: DNA-PKcs is critical for telomere capping. Proc Natl Acad Sci USA 98:15084–15088 (2001).
  31. Gravel S, Larrivee M, Labrecque P, Wellinger RJ: Yeast Ku as a regulator of chromosomal DNA end structure. Science 280:741–744 (1998).
  32. Green CM, Almouzni G: When repair meets chromatin. First in series on chromatin dynamics. EMBO Rep 3:28–33 (2002).
  33. Greer DA, Besley BD, Kennedy KB, Davey S: hRad9 rapidly binds DNA containing double-strand breaks and is required for damage-dependent topoisomerase II beta binding protein 1 focus formation. Cancer Res 63:4829–4835 (2003).
  34. Grunstein M: Histone acetylation in chromatin structure and transcription. Nature 389:349–352 (1997).
  35. Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, et al: Involvement of human MOF in ATM function. Mol Cell Biol 25:5292–5305 (2005).
  36. Hande MP, Balajee AS, Tchirkov A, Wynshaw-Boris A, Lansdorp PM: Extra-chromosomal telomeric DNA in cells from Atm(–/–) mice and patients with ataxia-telangiectasia. Hum Mol Genet 10:519–528 (2001).
  37. Hassa PO, Haenni SS, Elser M, Hottiger MO: Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70:789–829 (2006).
  38. Hassan AH, Prochasson P, Neely KE, Galasinski SC, Chandy M, et al: Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111:369–379 (2002).
  39. Hoeijmakers JH: DNA repair mechanisms. Maturitas 38:17–22 (2001).
  40. Hsu HL, Gilley D, Blackburn EH, Chen DJ: Ku is associated with the telomere in mammals. Proc Natl Acad Sci USA 96:12454–12458 (1999).
  41. Hsu JY, Sun ZW, Li X, Reuben M, Tatchel K, et al: Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102:279–291 (2000).
  42. Hunt CR, Pandita RK, Laszlo A, Higashikubo R, Agarwal M, et al: Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res 67:3010–3017 (2007).
  43. Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, et al: Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432:406–411 (2004).
  44. Jacobson RH, Ladurner AG, King DS, Tjian R: Structure and function of a human TAFII250 double bromodomain module. Science 288:1422–1425 (2000).
  45. Jason LJ, Moore SC, Lewis JD, Lindsey G, Ausio J: Histone ubiquitination: a tagging tail unfolds? Bioessays 24:166–174 (2002).
  46. Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, et al: ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8:37–45 (2006).
  47. Jenuwein T, Allis CD: Translating the histone code. Science 293:1074–1080 (2001).
  48. Jones DO, Cowell IG, Singh PB: Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays 22:124–137 (2000).
  49. Kanaar R, Hoeijmakers JH, van Gent DC: Molecular mechanisms of DNA double strand break repair. Trends Cell Biol 8:483–489 (1998).
  50. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T: P53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283:1321–1325 (1999).
  51. Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, et al: A phosphatase complex that dephosphorylates γH2AX regulates DNA damage checkpoint recovery. Nature 439:497–501 (2006).
  52. Kharbanda S, Kumar V, Dhar S, Pandey P, Chen C, et al: Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase. Curr Biol 10:568–575 (2000).
  53. Khorasanizadeh S: The nucleosome: from genomic organization to genomic regulation. Cell 116:259–272 (2004).
  54. Kishi S, Lu KP: A critical role for Pin2/TRF1 in ATM-dependent regulation. Inhibition of Pin2/TRF1 function complements telomere shortening, radiosensitivity, and the G(2)/M checkpoint defect of ataxia-telangiectasia cells. J Biol Chem 277:7420–7429 (2002).
  55. Kishi S, Zhou XZ, Ziv Y, Khoo C, Hill DE, et al: Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks. J Biol Chem 276:29282–29291 (2001).
  56. Kouzarides T: Histone methylation in transcriptional control. Curr Opin Genet Dev 12:198–209 (2002).
  57. Krishnamoorthy T, Chen X, Govin J, Cheung WL, Dorsey J, et al: Phosphorylation of histone H4 Ser1 regulates sporulation in yeast and is conserved in fly and mouse spermatogenesis. Genes Dev 20:2580–2592 (2006).
  58. Kuo MH, Allis CD: Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20:615–626 (1998).
  59. Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, et al: Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science 306:2084–2087 (2004).
  60. Lachner M, O’Sullivan RJ, Jenuwein T: An epigenetic road map for histone lysine methylation. J Cell Sci 116:2117–2124 (2003).
  61. Larrivee M, LeBel C, Wellinger RJ: The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex. Genes Dev 18:1391–1396 (2004).
  62. Lechner MS, Levitan I, Dressler GR: PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin. Nucleic Acids Res 28:2741–2751 (2000).
  63. Legube G, Trouche D: Regulating histone acetyltransferases and deacetylases. EMBO Rep 4:944–947 (2003).
  64. Li Y, Kirschmann DA, Wallrath LL: Does heterochromatin protein 1 always follow code? Proc Natl Acad Sci USA 99 Suppl 4:16462–16469 (2002).
  65. Lieberman HB, Hopkins KM, Nass M, Demetrick D, Davey S: A human homolog of the Schizosaccharomyces pomberad9+ checkpoint control gene. Proc Natl Acad Sci USA 93:13890–13895 (1996).
  66. Loizou JI, Murr R, Finkbeiner MG, Sawan C, Wang ZQ, Herceg Z: Epigenetic information in chromatin: the code of entry for DNA repair. Cell Cycle 5:696–701 (2006).
  67. Lombard DB, Guarente L: Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres. Cancer Res 60:2331–2334 (2000).
  68. Ludwig DL, Chen F, Peterson SR, Nussenzweig A, Li GC, Chen DJ: Ku80 gene expression is Sp1-dependent and sensitive to CpG methylation within a novel cis element. Gene 199:181–194 (1997).
  69. Lund AH, van Lohuizen M: Epigenetics and cancer. Genes Dev 18:2315–2335 (2004).
  70. Lydall D, Whitehall S: Chromatin and the DNA damage response. DNA Repair (Amst) 4:1195–1207 (2005).
  71. Macdonald N, Welburn JP, Noble ME, Nguyen A, Yaffe MB, et al: Molecular basis for the recognition of phosphorylated and phosphoacetylated histone H3 by 14-3-3. Mol Cell 20:199–211 (2005).
  72. Martin C, Zhang Y: The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6:838–849 (2005).
  73. Mimori T, Hardin JA, Steitz JA: Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. J Biol Chem 261:2274–2278 (1986).
  74. Nakamura TM, Moser BA, Russell P: Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. Genetics 161:1437–1452 (2002).
  75. Nakamura TM, Du LL, Redon C, Russell P: Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Mol Cell Biol 24:6215–6230 (2004).
  76. Narita M, Lowe SW: Senescence comes of age. Nat Med 11:920–922 (2005).
  77. Nowak SJ, Corces VG: Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Trends Genet 20:214–220 (2004).
  78. Nussenzweig A, Chen C, da Costa Soares V, Sanchez M, Sokol K, et al: Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382:551–555 (1996).
  79. Olins DE, Olins AL: Chromatin history: our view from the bridge. Nat Rev Mol Cell Biol 4:809–814 (2003).
  80. Osley MA: H2B ubiquitylation: the end is in sight. Biochim Biophys Acta 1677:74–78 (2004).
  81. Otten AD, Tapscott SJ: Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci USA 92:5465–5469 (1995).
  82. Paillard S, Strauss F: Analysis of the mechanism of interaction of simian Ku protein with DNA. Nucleic Acids Res 19:5619–5624 (1991).
  83. Pandita RK, Sharma GG, Laszlo A, Hopkins KM, Davey S, et al: Mammalian Rad9 plays a role in telomere stability, S- and G2-phase-specific cell survival, and homologous recombinational repair. Mol Cell Biol 26:1850–1864 (2006).
  84. Pandita TK: The role of ATM in telomere structure and function. Radiat Res 156:642–647 (2001).
  85. Pandita TK: ATM function and telomere stability. Oncogene 21:611–618 (2002a).
  86. Pandita TK: Telomeres and telomerase, in Bertino J (ed): Encyclopedia of Cancer Volume 4, pp 355–362 (Academic Press, Burlington 2002b).
  87. Pandita TK: A multifaceted role for ATM in genome maintenance: Expert Rev Mol Med 20:1–21 (2003).
  88. Pandita TK, Dhar S: Influence of ATM function on interactions between telomeres and nuclear matrix. Radiat Res 154:133–139 (2000).
  89. Pandita TK, Hittelman WN: The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia-telangiectasia. Radiat Res 131:214–223 (1992a).
  90. Pandita TK, Hittelman WN: Initial chromosome damage but not DNA damage is greater in ataxia telangiectasia cells. Radiat Res 130:94–103 (1992b).
  91. Pandita TK, Pathak S, Geard CR: Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells. Cytogenet Cell Genet 71:86–93 (1995).
  92. Pandita TK, Hall EJ, Hei TK, Piatyszek MA, Wright WE, et al: Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny. Oncogene 13:1423–1430 (1996).
  93. Pandita TK, Westphal CH, Anger M, Sawant SG, Geard CR, et al: ATM inactivation results in aberrant telomere clustering during meiotic prophase. Mol Cell Biol 19:5096–5105 (1999).
  94. Pandita TK, Hunt CR, Sharma GG, Yang Q: Regulation of telomere movement by telomere chromatin structure. Cell Mol Life Sci 64:131–138 (2007).
  95. Peterson CL, Cote J: Cellular machineries for chromosomal DNA repair. Genes Dev 18:602–616 (2004).
  96. Pisano S, Galati A, Cacchione S: Telomeric nucleosomes: forgotten players at chromosome ends. Cell Mol Life Sci 65:3553–3563 (2008).
  97. Pogribny I, Koturbash I, Tryndyak V, Hudson D, Stevenson SM, et al: Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. Mol Cancer Res 3:553–561 (2005).
  98. Porter SE, Greenwell PW, Ritchie KB, Petes TD: The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res 24:582–585 (1996).
  99. Pruss D, Bushman FD, Wolffe AP: Human immunodeficiency virus integrase directs integration to sites of severe DNA distortion within the nucleosome core. Proc Natl Acad Sci USA 91:5913–5917 (1994a).
  100. Pruss D, Reeves R, Bushman FD, Wolffe AP: The influence of DNA and nucleosome structure on integration events directed by HIV integrase. J Biol Chem 269:25031–25041 (1994b).
  101. Rice JC, Allis CD: Code of silence. Nature 414:258–261 (2001).
  102. Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, Kouzarides T: Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119:603–614 (2004).
  103. Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, et al: Active genes are tri-methylated at K4 of histone H3. Nature 419:407–411 (2002).
  104. Saunders WS, Chue C, Goebl M, Craig C, Clark RF, et al: Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. J Cell Sci 104:573–582 (1993).
  105. Scherthan H, Jerratsch M, Dhar S, Wang YA, Goff SP, Pandita TK: Meiotic telomere distribution and Sertoli cell nuclear architecture are altered in Atm- and Atm-p53-deficient mice. Mol Cell Biol 20:7773–7783 (2000).
  106. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd: SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 16:919–932 (2002).
  107. Scott SP, Pandita TK: The cellular control of DNA double-strand breaks. J Cell Biochem 99:1463–1475 (2006).
  108. Shafman T, Khanna KK, Kedar P, Spring K, Kozlov S, et al: Interaction between ATM protein and c-Abl in response to DNA damage. Nature 387:520–523 (1997).
  109. Sharma GG, Hwang KK, Pandita RK, Gupta A, Dhar S, et al: Human heterochromatin protein 1 isoforms HP1Hsα and HP1Hsβ interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation. Mol Cell Biol 23:8363–8376 (2003).
  110. Shiio Y, Eisenman RN: Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci USA 100:13225–13230 (2003).
  111. Shilatifard A: Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75:243–269 (2006).
  112. Sims RJ 3rd, Nishioka K, Reinberg D: Histone lysine methylation: a signature for chromatin function. Trends Genet 19:629–639 (2003).
  113. Singh PB, Miller JR, Pearce J, Kothary R, Burton RD, et al: A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res 19:789–794 (1991).
  114. Slijepcevic P: The role of DNA damage response proteins at telomeres – an ‘integrative’ model. DNA Repair (Amst) 5:1299–1306 (2006).
  115. Smilenov LB, Dhar S, Pandita TK: Altered telomere nuclear matrix interactions and nucleosomal periodicity in ataxia telangiectasia cells before and after ionizing radiation treatment. Mol Cell Biol 19:6963–6971 (1999).
  116. St Onge RP, Udell CM, Casselman R, Davey S: The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1. Mol Biol Cell 10:1985–1995 (1999).
  117. Stohr BA, Blackburn EH: ATM mediates cytotoxicity of a mutant telomerase RNA in human cancer cells. Cancer Res 68:5309–5317 (2008).
  118. Strahl BD, Allis CD: The language of covalent histone modifications. Nature 403:41–45 (2000).
  119. Strahl BD, Grant PA, Briggs SD, Sun ZW, Bone JR, et al: Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol Cell Biol 22:1298–1306 (2002).
  120. Sun Y, Jiang X, Chen S, Fernandes N, Price BD: A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci USA 102:13182–13187 (2005).
  121. Taccioli GE, Gottlieb TM, Blunt T, Priestley A, Demengeot J, et al: Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265:1442–1445 (1994).
  122. Takata H, Kanoh Y, Gunge N, Shirahige K, Matsuura A: Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol Cell 14:515–522 (2004).
  123. Takata H, Tanaka Y, Matsuura A: Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae. Mol Cell 17:573–583 (2005).
  124. Turner BM: Histone acetylation and an epigenetic code. Bioessays 22:836–845 (2000).
  125. van Attikum H, Gasser SM: The histone code at DNA breaks: a guide to repair? Nat Rev Mol Cell Biol 6:757–765 (2005).
  126. Venclovas C, Thelen MP: Structure-based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes. Nucleic Acids Res 28:2481–2493 (2000).
  127. Verdun RE, Crabbe L, Haggblom C, Karlseder J: Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell 20:551–561 (2005).
  128. Vidanes GM, Bonilla CY, Toczyski DP: Complicated tails: histone modifications and the DNA damage response. Cell 121:973–976 (2005).
  129. Wallrath LL, Lu Q, Granok H, Elgin SC: Architectural variations of inducible eukaryotic promoters: preset and remodeling chromatin structures. Bioessays 16:165–170 (1994).
  130. Winston F, Allis CD: The bromodomain: a chromatin-targeting module? Nat Struct Biol 6:601–604 (1999).
  131. Workman JL, Kingston RE: Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu Rev Biochem 67:545–579 (1998).
  132. Wreggett KA, Hill F, James PS, Hutchings A, Butcher GW, Singh PB: A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin. Cytogenet Cell Genet 66:99–103 (1994).
  133. Wu P, de Lange T: No overt nucleosome eviction at deprotected telomeres. Mol Cell Biol 28:5724–5735 (2008).
  134. Wurtele H, Verreault A: Histone post-translational modifications and the response to DNA double-strand breaks. Curr Opin Cell Biol 18:137–144 (2006).
  135. Xing H, Kornfeld K, Muslin AJ: The protein kinase KSR interacts with 14-3-3 protein and RAF. Curr Biol 7:294–300 (1997).
  136. Yan J, Jetten AM: RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites. Cancer Lett 271:179–190 (2008).
  137. Zhang Y: Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev 17:2733–2740 (2003).
  138. Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, et al: Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol 8:870–876 (2006).

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Abstract of Telomeres, DNA Damage Response and Genomic Instability

Received: September 15, 2008
Published online: January 30, 2009
Issue release date: February 2009

Number of Print Pages: 11
Number of Figures: 3
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR


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