Advertisement

Nucleotide Excision Repair: From Neurodegeneration to Cancer

  • Anastasios Liakos
  • Matthieu D. LavigneEmail author
  • Maria FousteriEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1007)

Abstract

DNA damage poses a constant threat to genome integrity taking a variety of shapes and arising by normal cellular metabolism or environmental insults. Human syndromes, characterized by increased cancer pre-disposition or early onset of age-related pathology and developmental abnormalities, often result from defective DNA damage responses and compromised genome integrity. Over the last decades intensive research worldwide has made important contributions to our understanding of the molecular mechanisms underlying genomic instability and has substantiated the importance of DNA repair in cancer prevention in the general population. In this chapter, we discuss Nucleotide Excision Repair pathway, the causative role of its components in disease-related pathology and recent technological achievements that decipher mutational landscapes and may facilitate pathological classification and personalized therapy.

Keywords

NER deficiency syndromes Genotype-phenotype relationship DNA damage responses Cancer genomics NER-associated somatic mutation landscapes Synthetic lethality 

References

  1. 1.
    Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JHJ (2014) Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol 15:465–481PubMedCrossRefGoogle Scholar
  3. 3.
    Roos WP, Thomas AD, Kaina B (2015) DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 16:20–33PubMedCrossRefGoogle Scholar
  4. 4.
    Roos WP, Kaina B (2006) DNA damage-induced cell death by apoptosis. Trends Mol Med 12:440–450PubMedCrossRefGoogle Scholar
  5. 5.
    Jeggo PA, Pearl LH, Carr AM (2016) DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer 16:35–42PubMedCrossRefGoogle Scholar
  6. 6.
    Nouspikel T (2009) DNA repair in mammalian cells: nucleotide excision repair: variations on versatility. Cell Mol Life Sci 66:994–1009PubMedCrossRefGoogle Scholar
  7. 7.
    Scharer OD (2013) Nucleotide excision repair in eukaryotes. Cold Spring Harb Perspect Biol 5:a012609PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Hanawalt PC, Spivak G (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9:958–970PubMedCrossRefGoogle Scholar
  9. 9.
    Gillet LCJ, Schärer OD (2006) Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev 106:253–276PubMedCrossRefGoogle Scholar
  10. 10.
    Scrima A et al (2008) Structural basis of UV DNA-damage recognition by the DDB1–DDB2 complex. Cell 135:1213–1223PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Tang J, Chu G (2002) Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein. DNA Repair 1:601–616PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Spivak G (2016) Transcription-coupled repair: an update. Arch Toxicol 90:2583–2594PubMedCrossRefGoogle Scholar
  13. 13.
    Vermeulen W, Fousteri M (2013) Mammalian transcription-coupled excision repair. Cold Spring Harb Perspect Biol 5:a012625PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Compe E, Egly J-M (2016) Nucleotide excision repair and transcriptional regulation: TFIIH and beyond. Annu Rev Biochem 85:265–290PubMedCrossRefGoogle Scholar
  15. 15.
    Ito S et al (2007) XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients. Mol Cell 26:231–243PubMedCrossRefGoogle Scholar
  16. 16.
    Staresincic L et al (2009) Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J 28:1111–1120PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Lehmann AR (2011) DNA polymerases and repair synthesis in NER in human cells. DNA Repair 10:730–733PubMedCrossRefGoogle Scholar
  18. 18.
    Ogi T et al (2010) Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol Cell 37:714–727PubMedCrossRefGoogle Scholar
  19. 19.
    Moser J et al (2007) Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase IIIα in a cell-cycle-specific manner. Mol Cell 27:311–323PubMedCrossRefGoogle Scholar
  20. 20.
    Smerdon MJ, Lieberman MW (1978) Nucleosome rearrangement in human chromatin during UV-induced DNA- repair synthesis. Proc Natl Acad Sci U S A 75:4238–4241PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Peterson CL, Almouzni G (2013) Nucleosome dynamics as modular systems that integrate DNA damage and repair. Cold Spring Harb Perspect Biol 5:a012658PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Cleaver JE, Lam ET, Revet I (2009) Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat Rev Genet 10:756–768PubMedCrossRefGoogle Scholar
  23. 23.
    Kraemer KH et al (2007) Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145:1388–1396PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Rapin I (2013) Handbook of clinical neurology (Dulac O, Lassonde M, Sarnat H, eds), vol 113. Elsevier, pp 1637–1650Google Scholar
  25. 25.
    Bradford PT et al (2011) Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet 48:168–176PubMedCrossRefGoogle Scholar
  26. 26.
    Masutani C et al (1999) The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature 399:700–704PubMedCrossRefGoogle Scholar
  27. 27.
    Fassihi H et al (2016) Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc Natl Acad Sci 113:E1236–E1245PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Brooks PJ (2013) Blinded by the UV light: how the focus on transcription-coupled NER has distracted from understanding the mechanisms of Cockayne syndrome neurologic disease. DNA Repair 12:656–671PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Cockayne EA (1936) Dwarfism with retinal atrophy and deafness. Arch Dis Child 11:1–8PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Cockayne EA (1946) Dwarfism with retinal atrophy and deafness. Arch Dis Child 21:52–54PubMedCentralCrossRefGoogle Scholar
  31. 31.
    Neill CA, Dingwall MM (1950) A syndrome resembling progeria: a review of two cases. Arch Dis Child 25:213–223PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kleijer WJ et al (2008) Incidence of DNA repair deficiency disorders in western Europe: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. DNA Repair 7:744–750PubMedCrossRefGoogle Scholar
  33. 33.
    Lehmann AR (1982) Three complementation groups in Cockayne syndrome. Mutat Res Mol Mech Mutagen 106:347–356CrossRefGoogle Scholar
  34. 34.
    Tanaka K, Kawai K, Kumahara Y, Ikenaga M, Okada Y (1981) Genetic complementation groups in Cockayne syndrome. Somatic Cell Genet 7:445–455PubMedCrossRefGoogle Scholar
  35. 35.
    Karikkineth AC, Scheibye-Knudsen M, Fivenson E, Croteau DL, Bohr VA (2017) Cockayne syndrome: clinical features, model systems and pathways. Ageing Res Rev 33:3–17PubMedCrossRefGoogle Scholar
  36. 36.
    Wilson BT et al (2016) The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genet Med 18:483–493PubMedCrossRefGoogle Scholar
  37. 37.
    Suzumura H, Arisaka O (2010) In: Ahmad SI (ed) Diseases of DNA repair. Springer, New York, pp 210–214. doi: 10.1007/978-1-4419-6448-9_19 CrossRefGoogle Scholar
  38. 38.
    Itoh T, Ono T, Yamaizumi M (1994) A new UV-sensitive syndrome not belonging to any complementation groups of xeroderma pigmentosum or Cockayne syndrome: siblings showing biochemical characteristics of Cockayne syndrome without typical clinical manifestations. Mutat Res Repair 314:233–248CrossRefGoogle Scholar
  39. 39.
    Horibata K et al (2004) Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome. Proc Natl Acad Sci U S A 101:15410–15415PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Nardo T et al (2009) A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage. Proc Natl Acad Sci 106:6209–6214PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Nakazawa Y et al (2012) Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Nat Genet 44:586–592PubMedCrossRefGoogle Scholar
  42. 42.
    Schwertman P et al (2012) UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair. Nat Genet 44:598–602PubMedCrossRefGoogle Scholar
  43. 43.
    Zhang X et al (2012) Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair. Nat Genet 44:593–597PubMedCrossRefGoogle Scholar
  44. 44.
    Fei J, Chen J (2012) KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in Transcription-coupled Repair (TCR). J Biol Chem 287:35118–35126PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Spivak G (2005) UV-sensitive syndrome. Mutat Res Mol Mech Mutagen 577:162–169CrossRefGoogle Scholar
  46. 46.
    Spivak G et al (2002) Ultraviolet-sensitive syndrome cells are defective in transcription-coupled repair of cyclobutane pyrimidine dimers. DNA Repair 1:629–643PubMedCrossRefGoogle Scholar
  47. 47.
    Schwertman P, Vermeulen W, Marteijn JA (2013) UVSSA and USP7, a new couple in transcription-coupled DNA repair. Chromosoma 122:275–284PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Oh K-S et al (2006) Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Hum Mutat 27:1092–1103PubMedCrossRefGoogle Scholar
  49. 49.
    Dietlein F, Thelen L, Reinhardt HC (2014) Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches. Trends Genet 30:326–339PubMedCrossRefGoogle Scholar
  50. 50.
    DiGiovanna JJ, Kraemer KH (2012) Shining a light on xeroderma pigmentosum. J Invest Dermatol 132:785–796PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Jeppesen DK, Bohr VA, Stevnsner T (2011) DNA repair deficiency in neurodegeneration. Prog Neurobiol 94:166–200PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Driver JA (2012) Understanding the link between cancer and neurodegeneration. J Geriatr Oncol 3:58–67CrossRefGoogle Scholar
  53. 53.
    McKinnon PJ (2013) Maintaining genome stability in the nervous system. Nat Neurosci 16:1523–1529PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Balajee AS, May A, Dianov GL, Friedberg EC, Bohr VA (1997) Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells. Proc Natl Acad Sci U S A 94:4306–4311PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    van den Boom V et al (2004) DNA damage stabilizes interaction of CSB with the transcription elongation machinery. J Cell Biol 166:27PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Dianov GL, Houle JF, Iyer N, Bohr VA, Friedberg EC (1997) Reduced RNA polymerase II transcription in extracts of Cockayne syndrome and xeroderma pigmentosum/Cockayne syndrome cells. Nucleic Acids Res 25:3636–3642PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    van Gool AJ, van der Horst GT, Citterio E, Hoeijmakers JH (1997) Cockayne syndrome: defective repair of transcription? EMBO J 16:4155–4162PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Selby CP, Sancar A (1997) Cockayne syndrome group B protein enhances elongation by RNA polymerase II. Proc Natl Acad Sci 94:11205–11209PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Tantin D, Kansal A, Carey M (1997) Recruitment of the putative transcription-repair coupling factor CSB/ERCC6 to RNA polymerase II elongation complexes. Mol Cell Biol 17:6803–6814PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Bradsher J et al (2002) CSB Is a component of RNA Pol I transcription. Mol Cell 10:819–829PubMedCrossRefGoogle Scholar
  61. 61.
    Yuan X, Feng W, Imhof A, Grummt I, Zhou Y (2007) Activation of RNA polymerase I transcription by Cockayne syndrome group B protein and histone methyltransferase G9a. Mol Cell 27:585–595PubMedCrossRefGoogle Scholar
  62. 62.
    Lee S-K, Yu S-L, Prakash L, Prakash S (2002) Requirement of yeast RAD2, a homolog of human XPG gene, for efficient RNA polymerase II transcription: implications for Cockayne syndrome. Cell 109:823–834PubMedCrossRefGoogle Scholar
  63. 63.
    Groisman R et al (2003) The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 113:357–367PubMedCrossRefGoogle Scholar
  64. 64.
    Assfalg R et al (2012) TFIIH is an elongation factor of RNA polymerase I. Nucleic Acids Res 40:650–659PubMedCrossRefGoogle Scholar
  65. 65.
    Koch S et al (2014) Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth. Cell Cycle 13:2029–2037PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Wang Y et al (2014) Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease. Proc Natl Acad Sci 111:14454–14459PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Wang Y et al (2016) Pharmacological bypass of Cockayne syndrome B function in neuronal differentiation. Cell Rep 14:2554–2561PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16:2–9PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Sollier J et al (2014) Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability. Mol Cell. doi: 10.1016/j.molcel.2014.10.020
  70. 70.
    Aguilera A, García-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46:115–124PubMedCrossRefGoogle Scholar
  71. 71.
    Nicolai S et al (2015) Identification of novel proteins co-purifying with Cockayne Syndrome Group B (CSB) reveals potential roles for CSB in RNA metabolism and chromatin dynamics. PLoS One 10:e0128558PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    El Hage A, French SL, Beyer AL, Tollervey D (2010) Loss of topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev 24:1546–1558PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Tuduri S et al (2009) Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol 11:1315–1324PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Sollier J, Cimprich KA (2015) Breaking bad: R-loops and genome integrity. Trends Cell Biol 25:514–522PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Groh M, Gromak N (2014) Out of balance: R-loops in human disease. PLoS Genet 10:e1004630PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Mazouzi A, Velimezi G, Loizou JI (2014) DNA replication stress: causes, resolution and disease. DNA Damage Repair 329:85–93Google Scholar
  77. 77.
    Ming G, Song H (2011) Adult neurogenesis in the Mammalian brain: significant answers and significant questions. Neuron 70:687–702PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997PubMedCrossRefGoogle Scholar
  79. 79.
    Aamann MD et al (2010) Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane. FASEB J 24:2334–2346PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Kamenisch Y et al (2010) Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging. J Exp Med 207:379–390PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Pascucci B et al (2012) An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress: alterations in oxidative metabolism in Cockayne. Aging Cell 11:520–529PubMedCrossRefGoogle Scholar
  82. 82.
    Scheibye-Knudsen M et al (2012) Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy. J Exp Med 209:855–869PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Fang EF et al (2014) Defective mitophagy in XPA via PARP-1 hyperactivation and NAD+/SIRT1 reduction. Cell 157:882–896PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Kruk PA, Rampino NJ, Bohr VA (1995) DNA damage and repair in telomeres: relation to aging. Proc Natl Acad Sci U S A 92:258–262PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Rochette PJ, Brash DE (2010) Human telomeres are hypersensitive to UV-induced DNA damage and refractory to repair. PLoS Genet 6:e1000926PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Kota LN et al (2015) Reduced telomere length in neurodegenerative disorders may suggest shared biology. J Neuropsychiatr Clin Neurosci 27:e92–e96CrossRefGoogle Scholar
  87. 87.
    Batenburg NL, Mitchell TRH, Leach DM, Rainbow AJ, Zhu X-D (2012) Cockayne syndrome group B protein interacts with TRF2 and regulates telomere length and stability. Nucleic Acids Res 40:9661–9674PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Jia P, Her C, Chai W (2015) DNA excision repair at telomeres. DNA Repair 36:137–145PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Clarke G et al (2000) A one-hit model of cell death in inherited neuronal degenerations. Nature 406:195–199PubMedCrossRefGoogle Scholar
  90. 90.
    Wu S, Powers S, Zhu W, Hannun YA (2015) Substantial contribution of extrinsic risk factors to cancer development. Nature 529:43–47PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Alexandrov LB et al (2013) Signatures of mutational processes in human cancer. Nature 500:415–421PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Haradhvala NJ et al (2016) Mutational strand asymmetries in cancer genomes reveal mechanisms of DNA damage and repair. Cell 164:538–549PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Helleday T, Eshtad S, Nik-Zainal S (2014) Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet 15:585–598PubMedCrossRefGoogle Scholar
  94. 94.
    Bryan DS, Ransom M, Adane B, York K, Hesselberth JR (2014) High resolution mapping of modified DNA nucleobases using excision repair enzymes. Genome Res 24:1534–1542PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Mao P, Meas R, Dorgan KM, Smerdon MJ (2014) UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation. Proc Natl Acad Sci 111:12811–12816PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Powell JR et al (2015) 3D-DIP-chip: a microarray-based method to measure genomic DNA damage. Sci Rep 5:7975PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Teng Y et al (2011) A novel method for the genome-wide high resolution analysis of DNA damage. Nucleic Acids Res 39:e10PubMedCrossRefGoogle Scholar
  98. 98.
    Zavala AG, Morris RT, Wyrick JJ, Smerdon MJ (2014) High-resolution characterization of CPD hotspot formation in human fibroblasts. Nucleic Acids Res 42:893–905PubMedCrossRefGoogle Scholar
  99. 99.
    Adar S, Hu J, Lieb JD, Sancar A (2016) Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis. Proc Natl Acad Sci 113:E2124–E2133PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Hu J, Adar S, Selby CP, Lieb JD, Sancar A (2015) Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution. Genes Dev 29:948–960PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    McGregor WG, Wei D, Maher VM, McCormick JJ (1999) Abnormal, error-prone bypass of photoproducts by xeroderma pigmentosum variant cell extracts results in extreme strand bias for the kinds of mutations induced by UV light. Mol Cell Biol 19:147–154PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Mitchell DL, Jen J, Cleaver JE (1992) Sequence specificity of cyclobutane pyrimidine dimers in DNA treated with solar (ultraviolet B) radiation. Nucleic Acids Res 20:225–229PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Douki T, Cadet J (2001) Individual determination of the yield of the main UV-induced dimeric pyrimidine photoproducts in DNA suggests a high mutagenicity of CC photolesions . Biochemistry (Mosc) 40:2495–2501CrossRefGoogle Scholar
  104. 104.
    Dumaz N, Drougard C, Sarasin A, Daya-Grosjean L (1993) Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients. Proc Natl Acad Sci 90:10529–10533PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Stary A, Kannouche P, Lehmann AR, Sarasin A (2003) Role of DNA polymerase η in the UV mutation spectrum in human cells. J Biol Chem 278:18767–18775PubMedCrossRefGoogle Scholar
  106. 106.
    Giglia G et al (1998) p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C. Cancer Res 58:4402PubMedGoogle Scholar
  107. 107.
    Kraemer KH, Lee MM, Scotto J (1984) DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum. Carcinogenesis 5:511–514PubMedCrossRefGoogle Scholar
  108. 108.
    Lawrence MS et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214–218PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Martincorena I, Campbell PJ (2015) Somatic mutation in cancer and normal cells. Science 349:1483–1489PubMedCrossRefGoogle Scholar
  110. 110.
    Petljak M, Alexandrov LB (2016) Understanding mutagenesis through delineation of mutational signatures in human cancer. Carcinogenesis 37:531–540PubMedCrossRefGoogle Scholar
  111. 111.
    Hollstein M, Alexandrov LB, Wild CP, Ardin M, Zavadil J (2017) Base changes in tumour DNA have the power to reveal the causes and evolution of cancer. Oncogene 36:158–167PubMedCrossRefGoogle Scholar
  112. 112.
    Pleasance ED et al (2010) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463:191–196PubMedCrossRefGoogle Scholar
  113. 113.
    Pleasance ED et al (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463:184–190PubMedCrossRefGoogle Scholar
  114. 114.
    Polak P et al (2013) Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair. Nat Biotechnol 32:71–75PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Perera D et al (2016) Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes. Nature 532:259–263PubMedCrossRefGoogle Scholar
  116. 116.
    Lahtz C, Pfeifer GP (2011) Epigenetic changes of DNA repair genes in cancer. J Mol Cell Biol 3:51–58PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Mombach JCM, Castro MAA, Moreira JCF, Almeida RMCD (2008) On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors. Genet Mol Res 7:152–160PubMedCrossRefGoogle Scholar
  118. 118.
    Alexandrov LB et al (2015) Clock-like mutational processes in human somatic cells. Nat Genet 47:1402–1407PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Kim J et al (2016) Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nat Genet 48:600–606PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    de Miranda NF et al (2013) DNA repair genes are selectively mutated in diffuse large B cell lymphomas. J Exp Med 210:1729PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Chae YK et al (2016) Genomic landscape of DNA repair genes in cancer. Oncotarget 7(17):23312–23321PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Caputo M et al (2013) The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth. DNA Repair 12:293–299PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Stamatoyannopoulos JA et al (2009) Human mutation rate associated with DNA replication timing. Nat Genet 41:393–395PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Helmrich A, Ballarino M, Nudler E, Tora L (2013) Transcription-replication encounters, consequences and genomic instability. Nat Struct Mol Biol 20:412–418PubMedCrossRefGoogle Scholar
  125. 125.
    Qiang L et al (2016) Autophagy positively regulates DNA damage recognition by nucleotide excision repair. Autophagy 12:357–368PubMedCrossRefGoogle Scholar
  126. 126.
    Liang C et al (2006) Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 8:688–698PubMedCrossRefGoogle Scholar
  127. 127.
    Yang Y et al (2016) Autophagic UVRAG promotes UV-induced photolesion repair by activation of the CRL4DDB2 E3 ligase. Mol Cell 62:507–519PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    White E (2012) Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12:401–410PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Velic D et al (2015) DNA damage signalling and repair inhibitors: the long-sought-after achilles’ heel of cancer. Biomol Ther 5:3204–3259Google Scholar
  130. 130.
    Curtin NJ (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12:801–817PubMedCrossRefGoogle Scholar
  131. 131.
    Jackson SP, Helleday T (2016) Drugging DNA repair. Science 352:1178–1179PubMedCrossRefGoogle Scholar
  132. 132.
    Olivier M, Hollstein M, Hainaut P (2010) TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2:a001008PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Ford JM, Hanawalt PC (1997) Expression of wild-type p53 is required for efficient global genomic nucleotide excision repair in UV-irradiated human fibroblasts. J Biol Chem 272:28073–28080PubMedCrossRefGoogle Scholar
  134. 134.
    Alexandrov LB, Stratton MR (2014) Mutational signatures: the patterns of somatic mutations hidden in cancer genomes. Cancer Genom 24:52–60Google Scholar
  135. 135.
    Chen W, Dong J, Haiech J, Kilhoffer M-C, Zeniou M (2016) Cancer stem cell quiescence and plasticity as major challenges in cancer therapy. Stem Cells Int 2016:1–16Google Scholar
  136. 136.
    Cicalese A et al (2009) The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138:1083–1095PubMedCrossRefGoogle Scholar
  137. 137.
    White AC, Lowry WE (2015) Refining the role for adult stem cells as cancer cells of origin. Trends Cell Biol 25:11–20PubMedCrossRefGoogle Scholar
  138. 138.
    Kreso A, Dick JE (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14:275–291PubMedCrossRefGoogle Scholar
  139. 139.
    Tomasetti C, Vogelstein B (2015) Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Ventura A et al (2007) Restoration of p53 function leads to tumour regression in vivo. Nature 445:661–665PubMedCrossRefGoogle Scholar
  141. 141.
    Wang Y et al (2011) Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation. J Clin Invest 121:893–904PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Guinea-Viniegra J et al (2012) Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17. J Clin Invest 122:2898–2910PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Adams PD, Jasper H, Rudolph KL (2015) Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell 16:601–612PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Barakat K, Tuszynski J (2013) New research directions in DNA repair. InTech, RijekaGoogle Scholar
  145. 145.
    Mouw KW, D’Andrea AD, Konstantinopoulos PA (2015) Nucleotide excision repair (NER) alterations as evolving biomarkers and therapeutic targets in epithelial cancers. Oncoscience 2:942PubMedPubMedCentralGoogle Scholar
  146. 146.
    Liu J, He C, Xing C, Yuan Y (2014) Nucleotide excision repair related gene polymorphisms and genetic susceptibility, chemotherapeutic sensitivity and prognosis of gastric cancer. Mutat Res Mol Mech Mutagen 765:11–21CrossRefGoogle Scholar
  147. 147.
    Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4:307–320PubMedCrossRefGoogle Scholar
  148. 148.
    Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584PubMedCrossRefGoogle Scholar
  149. 149.
    Chu G (1994) Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem 269:787–790PubMedGoogle Scholar
  150. 150.
    Koeppel F et al (2004) Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells. Clin Cancer Res 10:5604PubMedCrossRefGoogle Scholar
  151. 151.
    Earley JN, Turchi JJ (2011) Interrogation of nucleotide excision repair capacity: impact on platinum-based cancer therapy. Antioxid Redox Signal 14:2465–2477PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Calmels N et al (2016) Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing. Orphanet J Rare Dis 11:26PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Barakat KH et al (2012) Virtual screening and biological evaluation of inhibitors targeting the XPA-ERCC1 interaction. PLoS One 7:e51329PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Gentile F, Tuszynski JA, Barakat KH (2016) New design of nucleotide excision repair (NER) inhibitors for combination cancer therapy. J Mol Graph Model 65:71–82PubMedCrossRefGoogle Scholar
  155. 155.
    Mendoza J et al (2013) Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours. Br J Cancer 109:68–75PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Welsh C et al (2004) Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines: NER proteins in testis tumor cells. Int J Cancer 110:352–361PubMedCrossRefGoogle Scholar
  157. 157.
    Li Q et al (2000) Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res 20:645–652PubMedGoogle Scholar
  158. 158.
    Olaussen KA et al (2006) DNA repair by ERCC1 in non–small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355:983–991PubMedCrossRefGoogle Scholar
  159. 159.
    Stevens EV et al (2005) Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma. Cancer 103:2313–2319PubMedCrossRefGoogle Scholar
  160. 160.
    Weaver DA et al (2005) ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines. Mol Cancer 4:18PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Liu Y, Bernauer AM, Yingling CM, Belinsky SA (2012) HIF1 regulated expression of XPA contributes to cisplatin resistance in lung cancer. Carcinogenesis 33:1187–1192PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Arora S, Kothandapani A, Tillison K, Kalman-Maltese V, Patrick SM (2010) Downregulation of XPF–ERCC1 enhances cisplatin efficacy in cancer cells. DNA Repair 9:745–753PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Arora S et al (2016) Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells. Oncotarget 7(46):75104–75117PubMedPubMedCentralGoogle Scholar
  164. 164.
    Seiwert TY et al (2014) DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer. PLoS One 9:e102112PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Andrews BJ, Turchi JJ (2004) Development of a high-throughput screen for inhibitors of replication protein A and its role in nucleotide excision repair. Mol Cancer Ther 3:385PubMedCrossRefGoogle Scholar
  166. 166.
    Shuck SC, Turchi JJ (2010) Targeted inhibition of replication protein A reveals cytotoxic activity, synergy with chemotherapeutic DNA-damaging agents, and insight into cellular function. Cancer Res 70:3189–3198PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Mishra AK, Dormi SS, Turchi AM, Woods DS, Turchi JJ (2015) Chemical inhibitor targeting the replication protein A – DNA interaction increases the efficacy of Pt-based chemotherapy in lung and ovarian cancer. Biochem Pharmacol 93:25–33PubMedCrossRefGoogle Scholar
  168. 168.
    Furuta T et al (2002) Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res 62:4899PubMedGoogle Scholar
  169. 169.
    Aloyz R et al (2002) Regulation of cisplatin resistance and homologous recombinational repair by the TFIIH subunit XPD. Cancer Res 62:5457PubMedGoogle Scholar
  170. 170.
    Van Allen EM et al (2014) Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 4:1140PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Guo G et al (2013) Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet 45:1459–1463PubMedCrossRefGoogle Scholar
  172. 172.
    Weinstein JN et al (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315–322CrossRefGoogle Scholar
  173. 173.
    Ceccaldi R et al (2015) A unique subset of epithelial ovarian cancers with platinum sensitivity and PARP inhibitor resistance. Cancer Res 75:628–634PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Arora S et al (2015) Genetic variants that predispose to DNA double-strand breaks in lymphocytes from a subset of patients with familial colorectal carcinomas. Gastroenterology 149:1872–1883.e9PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Titov DV et al (2011) XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat Chem Biol 7:182–188PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Yi J-M et al (2016) Triptolide induces cell killing in multidrug-resistant tumor cells via CDK7/RPB1 rather than XPB or p44. Mol Cancer Ther 15:1495–1503PubMedCrossRefGoogle Scholar
  177. 177.
    Qu L et al (2015) Integrated targeted sphingolipidomics and transcriptomics reveal abnormal sphingolipid metabolism as a novel mechanism of the hepatotoxicity and nephrotoxicity of triptolide. J Ethnopharmacol 170:28–38PubMedCrossRefGoogle Scholar
  178. 178.
    Alekseev S et al (2014) A small molecule screen identifies an inhibitor of DNA repair inducing the degradation of TFIIH and the chemosensitization of tumor cells to platinum. Chem Biol 21:398–407PubMedCrossRefGoogle Scholar
  179. 179.
    Rizvi NA et al (2015) Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 348:124–128PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Castrén E, Elgersma Y, Maffei L, Hagerman R (2012) Treatment of neurodevelopmental disorders in adulthood. J Neurosci 32:14074PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Sakthiswary R, Raymond AA (2012) Stem cell therapy in neurodegenerative diseases: from principles to practice. Neural Regen Res 7:1822–1831PubMedPubMedCentralGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.Biomedical Sciences Research Center ‘Alexander Fleming’Vari, AthensGreece

Personalised recommendations