Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease

English version České info

Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G•C bp in the context of all 64 5′-NGNN-3′ motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines (ionization potentials). Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease.

Vyšlo v časopise: Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003816
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003816

Souhrn

Zdroje

1. LeyTJ, MardisER, DingL, FultonB, McLellanMD, et al. (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456: 66–72.

2. WoodLD, ParsonsDW, JonesS, LinJ, SjöblomT, et al. (2007) The genomic landscapes of human breast and colorectal cancers. Science 318: 1108–1113.

3. PuenteXS, PinyolM, QuesadaV, CondeL, OrdonezGR, et al. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475: 101–105.

4. WangK, KanJ, YuenST, ShiST, ChuKM, et al. (2011) Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 43: 1219–1223.

5. ParsonsDW, JonesS, ZhangX, LinJC-H, LearyRJ, et al. (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321: 1807–1812.

6. StranskyN, EgloffAM, TwardAD, KosticAD, CibulskisK, et al. (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333: 1157–1160.

7. AgrawalN, FrederickMJ, PickeringCR, BettegowdaC, ChangK, et al. (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333: 1154–1157.

8. LeeW, JiangZ, LiuJ, HavertyPM, GuanY, et al. (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465: 473–477.

9. PleasanceED, StephensPJ, O'MearaS, McBrideDJ, MeynertA, et al. (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463: 184–190.

10. WeiX, WaliaV, LinJC, TeerJK, PrickettTD, et al. (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43: 442–446.

11. PleasanceED, CheethamRK, StephensPJ, McBrideDJ, HumphraySJ, et al. (2010) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463: 191–196.

12. ChapmanMA, LawrenceMS, KeatsJJ, CibulskisK, SougnezC, et al. (2011) Initial genome sequencing and analysis of multiple myeloma. Nature 471: 467–472.

13. TCGARN (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474: 609–615.

14. BergerMF, LawrenceMS, DemichelisF, DrierY, CibulskisK, et al. (2011) The genomic complexity of primary human prostate cancer. Nature 470: 214–220.

15. KanZ, JaiswalBS, StinsonJ, JanakiramanV, BhattD, et al. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466: 869–873.

16. TotokiY, TatsunoK, YamamotoS, AraiY, HosodaF, et al. (2011) High-resolution characterization of a hepatocellular carcinoma genome. Nat Genet 43: 464–469.

17. BergerMF, HodisE, HeffernanTP, DeribeYL, LawrenceMS, et al. (2012) Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485: 502–506.

18. Nik-ZainalS, AlexandrovLB, WedgeDC, Van LooP, GreenmanCD, et al. (2012) Mutational processes molding the genomes of 21 breast cancers. Cell 149: 979–993.

19. IvanovD, HambySE, StensonPD, PhillipsAD, Kehrer-SawatzkiH, et al. (2011) Comparative analysis of germline and somatic microlesion mutational spectra in 17 human tumor suppressor genes. Hum Mutat 32: 620–632.

20. BaeleG, Van de PeerY, VansteelandtS (2008) A model-based approach to study nearest-neighbor influences reveals complex substitution patterns in non-coding sequences. Syst Biol 57: 675–692.

21. NikolaevSI, RimoldiD, IseliC, ValsesiaA, RobyrD, et al. (2012) Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat Genet 44: 133–139.

22. BurrowsCJ, MullerJG (1998) Oxidative nucleobase modifications leading to strand scission. Chem Rev 98: 1109–1152.

23. DizdarogluM (2012) Oxidatively induced DNA damage: Mechanisms, repair and disease. Cancer Lett 327: 26–47.

24. TurajlicS, FurneySJ, LambrosMB, MitsopoulosC, KozarewaI, et al. (2012) Whole genome sequencing of matched primary and metastatic acral melanomas. Genome Res 22: 196–207.

25. PfeiferGP, BesaratiniaA (2012) UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer. Photochem Photobiol Sci 11: 90–97.

26. CooperDN, BacollaA, FérecC, VasquezKM, Kehrer-SawatzkiH, et al. (2011) On the sequence-directed nature of human gene mutation: the role of genomic architecture and the local DNA sequence environment in mediating gene mutations underlying human inherited disease. Hum Mutat 32: 1075–1099.

27. MortonBR, CleggMT (1995) Neighboring base composition is strongly correlated with base substitution bias in a region of the chloroplast genome. J Mol Evol 41: 597–603.

28. LunterG, HeinJ (2004) A nucleotide substitution model with nearest-neighbour interactions. Bioinformatics 20 (Suppl 1) i216–223.

29. SiepelA, HausslerD (2004) Phylogenetic estimation of context-dependent substitution rates by maximum likelihood. Mol Biol Evol 21: 468–488.

30. ZhangW, BouffardGG, WallaceSS, BondJP (2007) Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. J Mol Evol 65: 207–214.

31. BaeleG, PeerYV, VansteelandtS (2009) Efficient context-dependent model building based on clustering posterior distributions for non-coding sequences. BMC Evol Biol 9: 87.

32. RobertsSA, SterlingJ, ThompsonC, HarrisS, MavD, et al. (2012) Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell 46: 424–435.

33. BurnsMB, LackeyL, CarpenterMA, RathoreA, LandAM, et al. (2013) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494: 366–370.

34. KrauthammerM, KongY, HaBH, EvansP, BacchiocchiA, et al. (2012) Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 44: 1006–1014.

35. BacollaA, WangG, JainA, ChuzhanovaNA, CerRZ, et al. (2011) Non-B DNA-forming sequences and WRN deficiency independently increase the frequency of base substitution in human cells. J Biol Chem 286: 10017–10026.

36. MurenNB, OlmonED, BartonJK (2012) Solution, surface, and single molecule platforms for the study of DNA-mediated charge transport. Phys Chem Chem Phys 14: 13754–13771.

37. CarmieliR, ZeidanTA, KelleyRF, MiQ, LewisFD, et al. (2009) Excited state, charge transfer, and spin dynamics in DNA hairpin conjugates with perylenediimide hairpin linkers. J Phys Chem A 113: 4691–4700.

38. WuY, YuanH, TanS, ChenJQ, TianD, et al. (2011) Increased complexity of gene structure and base composition in vertebrates. J Genet Genomics 38: 297–305.

39. LanderES, LintonLM, BirrenB, NusbaumC, ZodyMC, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

40. StarkMS, WoodsSL, GartsideMG, BonazziVF, Dutton-RegesterK, et al. (2012) Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat Genet 44: 165–169.

41. BravayaKB, KostkoO, DolgikhS, LandauA, AhmedM, et al. (2010) Electronic structure and spectroscopy of nucleic acid bases: ionization energies, ionization-induced structural changes, and photoelectron spectra. J Phys Chem A 114: 12305–12317.

42. SenthilkumarK, GrozemaFC, GuerraCF, BickelhauptFM, SiebbelesLDA (2003) Mapping the sites for selective oxidation of guanines in DNA. J Am Chem Soc 125: 13658–13659.

43. HutterMC (2006) Stability of the guanine-cytosine radical cation in DNA base pairs triplets. Chem Phys 326: 240–245.

44. SaitoI, NakamuraT, NakataniK, YoshiokaY, YamaguchiK, et al. (1998) Mapping of the hot spots for DNA damage by one-electron oxidation: Efficacy of GG doublets and GGG triplets as a trap in long-range hole migration. J Am Chem Soc 120: 12686–12687.

45. VoityukAA, JortnerJ, BixonM, RoschN (2000) Energetics of hole transfer in DNA. Chem Phys Lett 324: 430–434.

46. HallDB, HolmlinRE, BartonJK (1996) Oxidative DNA damage through long-range electron transfer. Nature 382: 731–735.

47. GieseB (2002) Long-distance electron transfer through DNA. Annu Rev Biochem 71: 51–70.

48. LewisFD, LiuXY, LiuJQ, HayesRT, WasielewskiMR (2000) Dynamics and equilibria for oxidation of G, GG, and GGG sequences in DNA hairpins. J Am Chem Soc 122: 12037–12038.

49. VoityukAA (2006) Estimation of electronic coupling in pi-stacked donor-bridge-acceptor systems: correction of the two-state model. J Chem Phys 124: 64505.

50. YakovchukP, ProtozanovaE, Frank-KamenetskiiMD (2006) Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34: 564–574.

51. FriedmanRA, HonigB (1995) A free energy analysis of nucleic acid base stacking in aqueous solution. Biophys J 69: 1528–1535.

52. BacollaA, LarsonJE, CollinsJR, LiJ, MilosavljevicA, et al. (2008) Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties. Genome Res 18: 1545–1553.

53. SchummS, PrevostM, Garcia-FresnadilloD, LentzenO, MoucheronC, et al. (2002) Influence of the sequence dependent ionization potentials of guanines on the luminescence quenching of Ru-labeled oligonucleotides: A theoretical and experimental study. J Phys Chem B 106: 2763–2768.

54. YokojimaS, YoshikiN, YanoiW, OkadaA (2009) Solvent effects on ionization potentials of guanine runs and chemically modified guanine in duplex DNA: effect of electrostatic interaction and its reduction due to solvent. J Phys Chem B 113: 16384–16392.

55. ConwellEM, BaskoDM (2001) Hole traps in DNA. J Am Chem Soc 123: 11441–11445.

56. SugiyamaH, SaitoI (1996) Theoretical studies of GC-specific photocleavage of DNA via electron transfer: Significant lowering of ionization potential and 5′-localization of HOMO of stacked GG bases in B-form DNA. J Am Chem Soc 118: 7063–7068.

57. ZaytsevaIL, TrofimovAB, SchirmerJ, PlekanO, FeyerV, et al. (2009) Theoretical and experimental study of valence-shell ionization spectra of guanine. J Phys Chem A 113: 15142–15149.

58. ParkJH, ChoiHY, ConwellEA (2004) Hole traps in DNA calculated with exponential electron-lattice coupling. J Phys Chem B 108: 19483–19486.

59. YoshiokaY, KitagawaY, TakanoY, YamaguchiK, NakamuraT, et al. (1999) Experimental and theoretical studies on the selectivity of GGG triplets toward one-electron oxidation in B-form DNA. J Am Chem Soc 121: 8712–8719.

60. RubinAF, GreenP (2009) Mutation patterns in cancer genomes. Proc Natl Acad Sci USA 106: 21766–21770.

61. GreenmanC, StephensP, SmithR, DalglieshGL, HunterC, et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446: 153–158.

62. PfeiferGP, BesaratiniaA (2009) Mutational spectra of human cancer. Hum Genet 125: 493–506.

63. LawrenceMS, StojanovP, PolakP, KryukovGV, CibulskisK, et al. (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499: 214–218.

64. MadisonAL, PerezZA, ToP, MaisonetT, RiosEV, et al. (2012) Dependence of DNA-protein cross-linking via guanine oxidation upon local DNA sequence as studied by restriction endonuclease inhibition. Biochemistry 51: 362–369.

65. AngelovD, BeylotB, SpasskyA (2005) Origin of the heterogeneous distribution of the yield of guanyl radical in UV laser photolyzed DNA. Biophys J 88: 2766–2778.

66. KupanA, SauliereA, BroussyS, SeguyC, PratvielG, et al. (2006) Guanine oxidation by electron transfer: one- versus two-electron oxidation mechanism. ChemBioChem 7: 125–133.

67. RokhlenkoY, GeacintovNE, ShafirovichV (2012) Lifetimes and reaction pathways of guanine radical cations and neutral guanine radicals in an oligonucleotide in aqueous solutions. J Am Chem Soc 134: 4955–4962.

68. MinkoIG, KozekovID, KozekovaA, HarrisTM, RizzoCJ, et al. (2008) Mutagenic potential of DNA-peptide crosslinks mediated by acrolein-derived DNA adducts. Mutat Res 637: 161–172.

69. GieseB, AmaudrutJ, KohlerAK, SpormannM, WesselyS (2001) Direct observation of hole transfer through DNA by hopping between adenine bases and by tunnelling. Nature 412: 318–320.

70. NakkenS, RodlandEA, RognesT, HovigE (2009) Large-scale inference of the point mutational spectrum in human segmental duplications. BMC Genomics 10: 43.

71. XieH, WangM, BischofJ, Bonaldo MdeF, SoaresMB (2009) SNP-based prediction of the human germ cell methylation landscape. Genomics 93: 434–440.

72. PanZ, HariharanM, ArkinJD, JalilovAS, McCullaghM, et al. (2011) Electron donor-acceptor interactions with flanking purines influence the efficiency of thymine photodimerization. J Am Chem Soc 133: 20793–20798.

73. BanyaszA, VayaI, Changenet-BarretP, GustavssonT, DoukiT, et al. (2011) Base pairing enhances fluorescence and favors cyclobutane dimer formation induced upon absorption of UVA radiation by DNA. J Am Chem Soc 133: 5163–5165.

74. CannistraroVJ, TaylorJS (2009) Acceleration of 5-methylcytosine deamination in cyclobutane dimers by G and its implications for UV-induced C-to-T mutation hotspots. J Mol Biol 392: 1145–1157.

75. HodisE, WatsonIR, KryukovGV, AroldST, ImielinskiM, et al. (2012) A landscape of driver mutations in melanoma. Cell 150: 251–263.

76. LawMH, MacgregorS, HaywardNK (2012) Melanoma genetics: recent findings take us beyond well-traveled pathways. J Invest Dermatol 132: 1763–1774.

77. SvilarD, GoellnerEM, AlmeidaKH, SobolRW (2011) Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage. Antioxid Redox Signal 14: 2491–2507.

78. HegdeML, ManthaAK, HazraTK, BhakatKK, MitraS, et al. (2012) Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases. Mech Ageing Dev 133: 157–168.

79. CreanC, ShaoJ, YunBH, GeacintovNE, ShafirovichV (2009) The role of one-electron reduction of lipid hydroperoxides in causing DNA damage. Chem Eur J 15: 10634–10640.

80. JaremDA, WilsonNR, DelaneyS (2009) Structure-dependent DNA damage and repair in a trinucleotide repeat sequence. Biochemistry 48: 6655–6663.

81. HanawaltPC, SpivakG (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9: 958–970.

82. ImielinskiM, BergerAH, HammermanPS, HernandezB, PughTJ, et al. (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150: 1107–1120.

83. GovindanR, DingL, GriffithM, SubramanianJ, DeesND, et al. (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150: 1121–1134.

84. Carrillo OesterreichF, BiebersteinN, NeugebauerKM (2011) Pause locally, splice globally. Trends Cell Biol 21: 328–335.

85. O'RaweJ, JiangT, SunG, WuY, WangW, et al. (2013) Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Med 5: 28.

86. GilissenC, HoischenA, BrunnerHG, VeltmanJA (2012) Disease gene identification strategies for exome sequencing. Eur J Hum Genet 20: 490–497.

87. MeachamF, BoffelliD, DhahbiJ, MartinDI, SingerM, et al. (2011) Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12: 451.

88. NakamuraK, OshimaT, MorimotoT, IkedaS, YoshikawaH, et al. (2011) Sequence-specific error profile of Illumina sequencers. Nucleic Acids Res 39: e90.

89. DerrienT, EstelleJ, Marco SolaS, KnowlesDG, RaineriE, et al. (2012) Fast computation and applications of genome mappability. PLoS One 7: e30377.

90. ZhengG, LuXJ, OlsonWK (2009) Web 3DNA–a web server for the analysis, reconstruction, and visualization of three-dimensional nucleic-acid structures. Nucleic Acids Res 37: W240–246.

91. WangJ, CieplakP, KollmanPA (2000) How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem 21: 1049–1074.

92. YangZ, LaskerK, Schneidman-DuhovnyD, WebbB, HuangCC, et al. (2012) UCSF Chimera, MODELLER, and IMP: An integrated modeling system. J Struct Biol 179: 269–278.

93. HessB, KutznerC, van der SpoelD, LindahlE (2008) GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4: 435–447.

94. KohnW, BeckeAD, ParrRG (1996) Density functional theory of electronic structure. J Phys Chem 100: 12974–12980.

95. ZhaoY, TruhlarDG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120: 215–241.

96. ZhaoY, TruhlarDG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41: 157–167.

97. HariharaPC, PopleJA (1973) Influence of polarization functions on molecular-orbital hydrogenation energies. Theor Chim Acta 28: 213–222.

98. FranclMM, PietroWJ, HehreWJ, BinkleyJS, GordonMS, et al. (1982) Self-consistent molecular-orbital methods .23. A polarization-type basis set for 2nd-row elements. J Chem Phys 77: 3654–3665.

99. SchmidtMW, BaldridgeKK, BoatzJA, ElbertST, GordonMS, et al. (1993) General atomic and molecular electronic-structure system. J Comput Chem 14: 1347–1363.

100. BodeBM, GordonMS (1998) MacMolPlt: A graphical user interface for GAMESS. J Mol Graphics Mod 16: 133–138.

101. YiM, MudunuriU, CheA, StephensRM (2009) Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis. BMC Bioinformatics 10: 200.

102. YiM, HortonJD, CohenJC, HobbsHH, StephensRM (2006) WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data. BMC Bioinformatics 7: 30.

103. FernandezA, GomezS (2008) Solving non-uniqueness in agglomerative hierarchical clustering using multidendrograms. J Classif 25: 43–65.