Elucidating Structure-Function Relationships in Bulky DNA Lesions: From Solution Structures to Polymerases

The Chemical Biology of DNA Damage

Volumn , Issue , 2010, Pages 331-352

  Broyde, Suse ^a   Wang, Lihua ^a   Patel, Dinshaw J ^b   Geacintov, Nicholas E ^a  

^a NEW YORK UNIVERSITY   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Benzo a pyrene DNA lesion; BF; Carcinogenesis; Computer simulation; Dpo4; Mutagenesis; Pol ; Polymerase crystal structure

Indexed keywords

EID: 84867972242     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527630110.ch14     Document Type: Chapter

References (109)

1. Luch, A. (2005) Nature and nurture-lessons from chemical carcinogenesis. Nat. Rev. Cancer, 5, 113-125.
2. Phillips, D.H. (1983) Fifty years of benzo(a)pyrene. Nature, 303, 468-472.
3. Clapp, R.W., Jacobs, M.M., and Loechler, E.L. (2008) Environmental and occupational causes of cancer: new evidence 2005-2007. Rev. Environ. Health, 23, 1-37.
4. Luch, A. (2006) The mode of action of organic carcinogens on cellular structures. EXS, 65-95.
5. Conney, A.H. (1982) Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. Cancer Res., 42, 4875-4917.
6. Cavalieri, E.L. and Rogan, E.G. (1995) Central role of radical cations in metabolic activation of polycyclic aromatic hydrocarbons. Xenobiotica, 25, 677-688.
7. Burczynski, M.E., Harvey, R.G., and Penning, T.M. (1998) Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7,8-dihydroxy-7,8-dihydrobenzo[ a ]pyrene to the activated o-quinone metabolite benzo[ a ] pyrene-7,8-dione. Biochemistry, 37, 6781-6790.
8. Buening, M.K., Wislocki, P.G., Levin, W., Yagi, H., Thakker, D.R., Akagi, H., Koreeda, M., Jerina, D.M., and Conney, A.H. (1978) Tumorigenicity of the optical enantiomers of the diastereomeric benzo[ a ]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7 β,8 α-dihydroxy-9 α,10 α-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene. Proc. Natl. Acad. Sci. USA, 75, 5358-5361.
9. Szeliga, J. and Dipple, A. (1998) DNA adduct formation by polycyclic aromatic hydrocarbon dihydrodiol epoxides. Chem. Res. Toxicol., 11, 1-11.
10. Cheng, S.C., Hilton, B.D., Roman, J.M., and Dipple, A. (1989) DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[ a ]pyrene dihydrodiol epoxide. Chem. Res. Toxicol., 2, 334-340.
11. Meehan, T. and Straub, K. (1979) Double-stranded DNA steroselectively binds benzo(a)pyrene diol epoxides. Nature, 277, 410-412.
12. Alekseyev, Y.O. and Romano, L.J. (2000) In vitro replication of primer-templates containing benzo[ a ]pyrene adducts by exonuclease-deficient Escherichia coli DNA polymerase I (Klenow fragment): effect of sequence context on lesion bypass. Biochemistry, 39, 10431-10438.
13. Hanrahan, C.J., Bacolod, M.D., Vyas, R.R., Liu, T., Geacintov, N.E., Loechler, E.L., and Basu, A.K. (1997) Sequence specific mutagenesis of the major (+)-anti-benzo[ a ]pyrene diol epoxide-DNA adduct at a mutational hot spot in vitro and in Escherichia coli cells. Chem. Res. Toxicol., 10, 369-377.
14. Zhuang, P., Kolbanovskiy, A., Amin, S., and Geacintov, N.E. (2001) Base sequence dependence of in vitro translesional DNA replication past a bulky lesion catalyzed by the exo-Klenow fragment of Pol I. Biochemistry, 40, 6660-6669.
15. Seo, K.Y., Nagalingam, A., Tiffany, M., and Loechler, E.L. (2005) Mutagenesis studies with four stereoisomeric N 2-dG benzo[ a ]pyrene adducts in the identical 5 ′-CGC sequence used in NMR studies: G → T mutations dominate in each case. Mutagenesis, 20, 441-448.
16. Seo, K.Y., Nagalingam, A., Miri, S., Yin, J., Chandani, S., Kolbanovskiy, A., Shastry, A., and Loechler, E.L. (2006) Mirror image stereoisomers of the major benzo[ a ]pyrene N 2-dG adduct are bypassed by different lesion-bypass DNA polymerases in E. coli. DNA Repair, 5, 515-522.
17. Shukla, R., Jelinsky, S., Liu, T., Geacintov, N.E., and Loechler, E.L. (1997) How stereochemistry affects mutagenesis by N 2-deoxyguanosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene: configuration of the adduct bond is more important than those of the hydroxyl groups. Biochemistry, 36, 13263-13269.
18. Rodriguez, H. and Loechler, E.L. (1995) Are base substitution and frameshift mutagenesis pathways interrelated? An analysis based upon studies of the frequencies and specificities of mutations induced by the (+)-anti diol epoxide of benzo[ a ]pyrene. Mutat. Res., 326, 29-37.
19. Moriya, M., Spiegel, S., Fernandes, A., Amin, S., Liu, T., Geacintov, N., and Grollman, A.P. (1996) Fidelity of tran slesional synthesis past benzo[ a ] pyrene diol epoxide-2 ′-deoxyguanosine DNA adducts: marked effects of host cell, sequence context, and chirality. Biochemistry, 35, 16646-16651.
20. Jelinsky, S.A., Liu, T., Geacintov, N.E., and Loechler, E.L. (1995) The major, N 2-Gua adduct of the (+)-anti-benzo[ a ] pyrene diol epoxide is capable of inducing G → A and G → C, in addition to G → T, mutations. Biochemistry, 34, 13545-13553.
21. Shen, X., Sayer, J.M., Kroth, H., Ponten, I., O'Donnell, M., Woodgate, R., Jerina, D.M., and Goodman, M.F. (2002) Efficiency and accuracy of SOS-induced DNA polymerases replicating benzo[ a ]pyrene-7,8-diol 9,10-epoxide A and G adducts. J. Biol. Chem., 277, 5265-5274.
22. Fernandes, A., Liu, T., Amin, S., Geacintov, N.E., Grollman, A.P., and Moriya, M. (1998) Mutagenic potential of stereoisomeric bay region (+)-and (-)-cis-anti-benzo[ a ]pyrene diol epoxide-N 2-2 ′-deoxyguanosine adducts in Escherichia coli and simian kidney cells. Biochemistry, 37, 10164-10172.
23. Zhao, B., Wang, J., Geacintov, N.E., and Wang, Z. (2006) Pol η, Pol ζ and Rev1 together are required for G to T transversion mutations induced by the (+)-and (-)-trans-anti-BPDE-N 2-dG DNA adducts in yeast cells. Nucleic Acids Res., 34, 417-425.
24. Avkin, S., Goldsmith, M., Velasco-Miguel, S., Geacintov, N., Friedberg, E.C., and Livneh, Z. (2004) Quantitative analysis of translesion DNA synthesis across a benzo[ a ]pyrene-guanine adduct in mammalian cells: the role of DNA polymerase κ. J. Biol. Chem., 279, 53298-53305.
25. Geacintov, N.E., Gagliano, A.G., Ibanez, V., and Harvey, R.G. (1982) Spectroscopic characterizations and comparisons of the structures of the covalent adducts derived from the reactions of 7,8-dihydroxy-7,8,9,10-tetrahydrobenzo [ a ]pyrene-9,10-oxide, and the 9,10-epoxides of 7,8,9,10-tetrahydrobenzo[ a ] pyrene and 9,10,11,12-tetrahydrobenzo [ e ]pyrene with DNA. Carcinogenesis, 3, 247-253.
26. Geacintov, N.E., Yoshida, H., Ibanez, V., Jacobs, S.A., and Harvey, R.G. (1984) Conformations of adducts and kinetics of binding to DNA of the optically pure enantiomers of anti-benzo(a)pyrene diol epoxide. Biochem. Biophys. Res. Commun., 122, 33-39.
27. Harvey, R.G. and Geacintov, N.E. (1988) Intercalation and binding of carcinogenic hydrocarbon metabolites to nucleic acids. Acc. Chem. Res., 21, 66-73.
28. Singh, S.B., Hingerty, B.E., Singh, U.C., Greenberg, J.P., Geacintov, N.E., and Broyde, S. (1991) Structures of the (+)-and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene adducts to guanine-N 2 in a duplex dodecamer. C ancer Res., 51, 3482-3492.
29. Tan, J., Geacintov, N.E., and Broyde, S. (2000) Conformational determinants of structures in stereoisomeric cis-opened anti-benzo[ a ]pyrene diol epoxide adducts to adenine in DNA. Chem. Res. Toxicol., 13, 811-822.
30. Tan, J., Geacintov, N.E., and Broyde, S. (2000) Principles governing conformations in stereoisomeric adducts of bay region benzo[ a ]pyrene diol epoxides to adenine in DNA: steric and hydrophobic effects are dominant. J. Am. Chem. Soc., 122, 3021-3032.
31. Wu, M., Yan, S.F., Tan, J., Patel, D.J., Geacintov, N.E., and Broyde, S. (2004) Conformational searches elucidate effects of stereochemistry on structures of deoxyadenosine covalently bound to tumorigenic metabolites of benzo[ c ]phenanthrene. Front. Biosci., 9, 2807-2818.
32. Xie, X.M., Geacintov, N.E., and Broyde, S. (1999) Origins of conformational differences between cis and trans DNA adducts derived from enantiomeric anti-benzo[ a ]pyrene diol epoxides. Chem. Res. Toxicol., 12, 597-609.
33. Xie, X.M., Geacintov, N.E., and Broyde, S. (1999) Stereochemical origin of opposite orientations in DNA adducts derived from enantiomeric anti-benzo[ a ] pyrene diol epoxides with different tumorigenic potentials. Biochemistry, 38, 2956-2968.
34. de los Santos, C., Cosman, M., Hingerty, B.E., Ibanez, V., Margulis, L.A., Geacintov, N.E., Broyde, S., and Patel, D.J. (1992) Infl uence of benzo[ a ] pyrene diol epoxide chirality on solution conformations of DNA covalent adducts: the (-)-trans-anti-[BP]G · C adduct structure and comparison with the (+)-trans-anti-[BP]G · C enantiomer. Biochemistry, 31, 5245-5252.
35. Geacintov, N.E., Cosman, M., Hingerty, B.E., Amin, S., Broyde, S., and Patel, D.J. (1997) NMR solution structures of stereoisometric covalent polycyclic aromatic carcinogen-DNA adduct: principles, patterns, and diversity. Chem. Res. Toxicol., 10, 111-146.
36. Cosman, M., de los Santos, C., Fiala, R., Hingerty, B.E., Singh, S.B., Ibanez, V., Margulis, L.A., Live, D., Geacintov, N.E., Broyde, S., et al. (1992) Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[ a ] pyrene diol epoxide and DNA. Proc. Natl. Acad. Sci. USA, 89, 1914-1918.
37. Broyde, S., Wang, L., Zhang, L., Rechkoblit, O., Geacintov, N.E., and Patel, D.J. (2008) DNA adduct structure-function relationships: comparing solution with polymerase structures. Chem. Res. Toxicol., 21, 45-52.
38. Karle, I.L., Yagi, H., Sayer, J.M., and Jerina, D.M. (2004) Crystal and molecular structure of a benzo[ a ]pyrene 7,8-diol 9,10-epoxide N 2-deoxyguanosine adduct: absolute configuration and conformation. Proc. Natl. Acad. Sci. USA, 101, 1433-1438.
39. Lukin, M. and de Los Santos, C. (2006) NMR structures of damaged DNA. Chem. Rev., 106, 607-686.
40. Geacintov, N.E. (1988) Mechanisms of reaction of polycyclic aromatic epoxide derivatives with nucleic acids, in Polycyclic Aromatic Hydrocarbon Carcinogenesis: Structure-Activity Relationships, vol. II (eds S.K. Yang and B.D. Silverman), CRC Press, Boca Raton, FL, pp. 181-206.
41. Cosman, M., de los Santos, C., Fiala, R., Hingerty, B.E., Ibanez, V., Luna, E., Harvey, R., Geacintov, N.E., Broyde, S., and Patel, D.J. (1993) Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: intercalation of the covalently attached benzo[ a ] pyrenyl ring into the helix and displacement of the modified deoxyguanosine. Biochemistry, 32, 4145-4155.
42. Cosman, M., Hingerty, B.E., Luneva, N., Amin, S., Geacintov, N.E., Broyde, S., and Patel, D.J. (1996) Solution conformation of the (-)-cis-anti-benzo[ a ] pyrenyl-dG adduct opposite dC in a DNA duplex: intercalation of the covalently attached BP ring into the helix with base displacement of the modified deoxyguanosine into the major groove. Biochemistry, 35, 9850-9863.
43. Yan, S., Shapiro, R., Geacintov, N.E., and Broyde, S. (2001) Stereochemical, structural, and thermodynamic origins of stability differences between stereoisomeric benzo[ a ]pyrene diol epoxide deoxyadenosine adducts in a DNA mutational hot spot sequence. J. Am. Chem. Soc., 123, 7054-7066.
44. Perlow-Poehnelt, R.A., Likhterov, I., Scicchitano, D.A., Geacintov, N.E., and Broyde, S. (2004) The spacious active site of a Y-family DNA polymerase facilitates promiscuous nucleotide incorporation opposite a bulky carcinogen-DNA adduct: elucidating the structure-function relationship through experimental and computational approaches. J. Biol. Chem., 279, 36951-36961.
45. Chary, P. and Lloyd, R.S. (1995) In vitro replication by prokaryotic and eukaryotic polymerases on DNA templates containing site-specific and stereospecific benzo[ a ]pyrene-7,8-dihydrodiol-9,10-epoxide adducts. Nucleic Acids Res., 23, 1398-1405.
46. Shibutani, S., Margulis, L.A., Geacintov, N.E., and Grollman, A.P. (1993) Translesional synthesis on a DNA template containing a single stereoisomer of dG-(+)-or dG-(-)-anti-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene). Biochemistry, 32, 7531-7541.
47. Rechkoblit, O., Zhang, Y., Guo, D., Wang, Z., Amin, S., Krzeminsky, J., Louneva, N., and Geacintov, N.E. (2002) trans-Lesion synthesis past bulky benzo[ a ]pyrene diol epoxide N 2-dG and N 6-dA lesions catalyzed by DNA bypass polymerases. J. Biol. Chem., 277, 30488-30494.
48. Mocquet, V., Kropachev, K., Kolbanovskiy, M., Kolbanovskiy, A., Tapias, A., Cai, Y., Broyde, S., Geacintov, N.E., and Egly, J.M. (2007) The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[ a ]pyrenyl-DNA lesions. EMBO J., 26, 2923-2932.
49. Schinecker, T.M., Perlow, R.A., Broyde, S., Geacintov, N.E., and Scicchitano, D.A. (2003) Human RNA polymerase II is partially blocked by DNA adducts derived from tumorigenic benzo[ c ] phenanthrene diol epoxides: relating biological consequences to conformational preferences. Nucleic Acids Res., 31, 6004-6015.
50. Perlow, R.A., Kolbanovskii, A., Hingerty, B.E., Geacintov, N.E., Broyde, S., and Scicchitano, D.A. (2002) DNA adducts from a tumorigenic metabolite of benzo[ a ]pyrene block human RNA polymerase II elongation in a sequence-and stereochemistry-dependent manner. J. Mol. Biol., 321, 29-47.
51. Bauer, J., Xing, G., Yagi, H., Sayer, J.M., Jerina, D.M., and Ling, H. (2007) A structural gap in Dpo4 supports mutagenic bypass of a major benzo[ a ] pyrene dG adduct in DNA through template misalignment. Proc. Natl. Acad. Sci. USA, 104, 14905-14910.
52. Ling, H., Sayer, J.M., Plosky, B.S., Yagi, H., Boudsocq, F., Woodgate, R., Jerina, D.M., and Yang, W. (2004) Crystal structure of a benzo[ a ]pyrene diol epoxide adduct in a ternary complex with a DNA polymerase. Proc. Natl. Acad. Sci. USA, 101, 2265-2269.
53. Broyde, S., Wang, L., Rechkoblit, O., Geacintov, N.E., and Patel, D.J. (2008) Lesion processing: high-fidelity versus lesion-bypass DNA polymerases. Trends Biochem. Sci., 33, 209-219.
54. Choi, J.Y. and Guengerich, F.P. (2004) Analysis of the effect of bulk at N 2-alkylguanine DNA adducts on catalytic efficiency and fidelity of the processive DNA polymerases bacteriophage T7 exonuclease-and HIV-1 reverse transcriptase. J. Biol. Chem., 279, 19217-19229.
55. Xu, P., Oum, L., Beese, L.S., Geacintov, N.E., and Broyde, S. (2007) Following an environmental carcinogen N 2-dG adduct through replication: elucidating blockage and bypass in a high-fidelity DNA polymerase. Nucleic Acids Res., 35, 4275-4288.
56. Pages, V. and Fuchs, R.P. (2002) How DNA lesions are turned into mutations within cells? Oncogene, 21, 8957-8966.
57. Friedberg, E.C., Lehmann, A.R., and Fuchs, R.P. (2005) Trading places: howdo DNA polymerases switch during translesion DNA synthesis? Mol. Cell, 18, 499-505.
58. Lehmann, A.R., Niimi, A., Ogi, T., Brown, S., Sabbioneda, S., Wing, J.F., Kannouche, P.L., and Green, C.M. (2007) Translesion synthesis: Y-family polymerases and the polymerase switch. DNA Repair, 6, 891-899.
59. Friedberg, E.C., Wagner, R., and Radman, M. (2002) Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science, 296, 1627-1630.
60. Prakash, S., Johnson, R.E., and Prakash, L. (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem., 74, 317-353.
61. Yang, W. and Woodgate, R. (2007) What a difference a decade makes: insights into translesion DNA synthesis. Proc. Natl. Acad. Sci. USA, 104, 15591-15598.
62. Goodman, M.F. (2002) Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu. Rev. Biochem., 71, 17-50.
63. Waters, L.S., Minesinger, B.K., Wiltrout, M.E., D'Souza, S., Woodruff, R.V., and Walker, G.C. (2009) Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. M icrobiol. Mol. Biol. Rev., 73, 134-154.
64. Steitz, T.A. (1998) A mechanism for all polymerases. Nature, 391, 231-232.
65. Rechkoblit, O., Malinina, L., Cheng, Y., Kuryavyi, V., Broyde, S., Geacintov, N.E., and Patel, D.J. (2006) Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion. PLoS Biol., 4, e11.
66. Rothwell, P.J. and Waksman, G. (2005) Structure and mechanism of DNA polymerases. Adv. Protein Chem., 71, 401-440.
67. Johnson, S.J., Taylor, J.S., and Beese, L.S. (2003) Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations. Proc. Natl. Acad. Sci. USA, 100, 3895-3900.
68. Hsu, G.W., Huang, X., Luneva, N.P., Geacintov, N.E., and Beese, L.S. (2005) Structure of a high fidelity DNA polymerase bound to a benzo[ a ]pyrene adduct that blocks replication. J. Biol. Chem., 280, 3764-3770.
69. Perlow, R.A. and Broyde, S. (2001) Evading the proofreading machinery of a replicative DNA polymerase: induction of a mutation by an environmental carcinogen. J. Mol. Biol., 309, 519-536.
70. Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Crystal structure of a Y-family DNA polymerase in action: a mechanism for error-prone and lesion-bypass replication. Cell, 107, 91-102.
71. Xu, P., Oum, L., Geacintov, N.E., and Broyde, S. (2008) Nucleotide selectivity opposite a benzo[ a ]pyrene-derived N 2-dG adduct in a Y-family DNA polymerase: a 5 ′-slippage mechanism. Biochemistry, 47, 2701-2709.
72. Boudsocq, F., Iwai, S., Hanaoka, F., and Woodgate, R. (2001) Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic polh. Nucleic Acids Res., 29, 4607-4616.
73. Oum, L. (2007) Base-sequence and temperature effects on in vitro studies of translesion synthesis past anti-BPDE-N 2-dG adducts, PhD Thesis, New York University.
74. Xu, P., Oum, L., Geacintov, N.E., and Broyde, S. (2009) Visualizing sequence-governed nucleotide selectivities and mutagenic consequences through a replicative cycle: processing of a bulky carcinogen N 2-dG lesion in a Y-family polymerase. Biochemistry, 48, 4677-4690.
75. Mizukami, S., Kim, T.W., Helquist, S.A., and Kool, E.T. (2006) Varying DNA base-pair size in subangstrom increments: evidence for a loose, not large, active site in low-fidelity Dpo4 polymerase. Biochemistry, 45, 2772-2778.
76. Streisinger, G., Okada, Y., Emrich, J., Newton, J., Tsugita, A., Terzaghi, E., and Inouye, M. (1966) Frameshift mutations and the genetic code. Cold Spring Harb. Symp. Quant. Biol., 31, 77-84.
77. Kunkel, T.A. (1990) Misalignment-mediated DNA synthesis errors. Biochemistry, 29, 8003-8011.
78. Kunkel, T.A. (1992) DNA replication fidelity. J. Biol. Chem., 267, 18251-18254.
79. Ripley, L.S. (1990) Frameshift mutation: determinants of specificity. Annu. Rev. Genet., 24, 189-213.
80. Lone, S., Townson, S.A., Uljon, S.N., Johnson, R.E., Brahma, A., Nair, D.T., Prakash, S., Prakash, L., and Aggarwal, A.K. (2007) Human DNA polymerase κ encircles DNA: implications for mismatch extension and lesion bypass. Mol. Cell, 25, 601-614.
81. Suzuki, N., Ohashi, E., Kolbanovskiy, A., Geacintov, N.E., Grollman, A.P., Ohmori, H., and Shibutani, S. (2002) Translesion synthesis by human DNA polymerase κ on a DNA template containing a single stereoisomer of dG-(+)-or dG-(-)-anti-N 2-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene). Biochemistry, 41, 6100-6106.
82. Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., and Wang, Z. (2002) Activities of human DNA polymerase κ in response to the major benzo[ a ]pyrene DNA adduct: error-free lesion bypass and extension synthesis from opposite the lesion. DNA Repair, 1, 559-569.
83. Huang, X., Kolbanovskiy, A., Wu, X., Zhang, Y., Wang, Z., Zhuang, P., Amin, S., and Geacintov, N.E. (2003) Effects of base sequence context on translesion synthesis past a bulky (+)-trans-anti-B[ a ]P-N 2-dG lesion catalyzed by the Y-family polymerase pol κ. Biochemistry, 42, 2456-2466.
84. Choi, J.Y., Angel, K.C., and Guengerich, F.P. (2006) Translesion synthesis across bulky N 2-alkyl guanine DNA adducts by human DNA polymerase κ. J. Biol. Chem., 281, 21062-21072.
85. Poon, K., Itoh, S., Suzuki, N., Laxmi, Y.R., Yoshizawa, I., and Shibutani, S. (2008) Miscoding properties of 6 α-and 6 β-diastereoisomers of the N 2-(estradiol-6-yl)-2 ′-deoxyguanosine DNA adduct by Y-family human DNA polymerases. Biochemistry, 47, 6695-6701.
86. Yasui, M., Dong, H., Bonala, R.R., Suzuki, N., Ohmori, H., Hanaoka, F., Johnson, F., Grollman, A.P., and Shibutani, S. (2004) Mutagenic properties of 3-(deoxyguanosin-N 2-yl)-2-acetylaminofl uorene, a persistent acetylaminofl uorene-derived DNA adduct in mammalian cells. Biochemistry, 43, 15005-15013.
87. Jia, L., Geacintov, N.E., and Broyde, S. (2008) The N-clasp of human DNA polymerase κ promotes blockage or error-free bypass of adenine-or guanine-benzo[ a ]pyrenyl lesions. Nucleic Acids Res., 36, 6571-6584.
88. Choi, J.Y., Chowdhury, G., Zang, H., Angel, K.C., Vu, C.C., Peterson, L.A., and Guengerich, F.P. (2006) Translesion synthesis across O 6-alkylguanine DNA adducts by recombinant human DNA polymerases. J. Biol. Chem., 281, 38244-38256.
89. Wang, Y. and Schlick, T. (2008) Quantum mechanics/molecular mechanics investigation of the chemical reaction in Dpo4 reveals water-dependent pathways and requirements for active site reorganization. J. Am. Chem. Soc., 130, 13240-13250.
90. Lin, P., Pedersen, L.C., Batra, V.K., Beard, W.A., Wilson, S.H., and Pedersen, L.G. (2006) Energy analysis of chemistry for correct insertion by DNA polymerase β. Proc. Natl. Acad. Sci. USA, 103, 13294-13299.
91. Florian, J., Goodman, M.F., and Warshel, A. (2005) Computer simulations of protein functions: searching for the molecular origin of the replication fidelity of DNA polymerases. Proc. Natl. Acad. Sci. USA, 102, 6819-6824.
92. Hu, H. and Yang, W. (2008) Free energies of chemical reactions in solution and in enzymes with ab initio quantum mechanics/molecular mechanics methods. Annu. Rev. Phys. Chem., 59, 573-601.
93. Zhang, Y., Liu, H., and Yang, W. (2000) Free energy calculation on enzyme reactions with an efficient iterative procedure to determine minimum energy paths on a combined ab initio QM/MM potential energy surface. J. Chem. Phys., 112, 3483-3492.
94. Zhang, Y., Lee, T., and Yang, W. (1999) A pseudobond approach to combining quantum mechanical and molecular mechanical methods. J. Chem. Phys., 110, 46-54.
95. Zhang, Y. (2005) Improved pseudobonds for combined ab initio quantum mechanical/molecular mechanical methods. J. Chem. Phys., 122, 024114.
96. Wang, L., Yu, X., Hu, P., Broyde, S., and Zhang, Y. (2007) A water-mediated and substrate-assisted catalytic mechanism for Sulfolobus solfataricus DNA polymerase IV. J. Am. Chem. Soc., 129, 4731-4737.
97. Wang, L., Broyde, S., and Zhang, Y. (2009) Polymerase-tailored variations in the water-mediated and substrate-assisted mechanism for nucleotidyl transfer: insights from a study of T7 DNA polymerase. J. Mol. Biol., 389, 787-796.
98. Castro, C., Smidansky, E., Maksimchuk, K.R., Arnold, J.J., Korneeva, V.S., Gotte, M., Konigsberg, W., and Cameron, C.E. (2007) Two proton transfers in the transition state for nucleotidyl transfer catalyzed by RNA-and DNA-dependent RNA and DNA polymerases. Proc. Natl. Acad. Sci. USA, 104, 4267-4272.
99. Castro, C., Smidansky, E.D., Arnold, J.J., Maksimchuk, K.R., Moustafa, I., Uchida, A., Gotte, M., Konigsberg, W., and Cameron, C.E. (2009) Nucleic acid polymerases use a general acid for nucleotidyl transfer. Nat. Struct. Mol. Biol., 16, 212-218.
100. Florian, J., Goodman, M.F., and Warshel, A. (2003) Computer simulation of the chemical catalysis of DNA polymerases: discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymerase. J. Am. Chem. Soc., 125, 8163-8177.
101. Radhakrishnan, R. and Schlick, T. (2006) Correct and incorrect nucleotide incorporation pathways in DNA polymerase b. Biochem. Biophys. Res. Commun., 350, 521-529.
102. Bojin, M.D. and Schlick, T. (2007) A quantum mechanical investigation of possible mechanisms for the nucleotidyl transfer reaction catalyzed by DNA polymerase β. J. Phys. Chem. B, 111, 11244-11252.
103. Cisneros, G.A., Perera, L., Garcia-Diaz, M., Bebenek, K., Kunkel, T.A., and Pedersen, L.G. (2008) Catalytic mechanism of human DNA polymerase l with Mg 2+ and Mn 2+ from ab initio quantum mechanical/molecular mechanical studies. DNA Repair, 7, 1824-1834.
104. Wang, S., Hu, P., and Zhang, Y. (2007) Ab initio quantum mechanical/ molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9. J. Phys. Chem. B, 111, 3758-3764.
105. de Bruin, R.A., Kalashnikova, T.I., Aslanian, A., Wohlschlegel, J., Chahwan, C., Yates, J.R., 3rd, Russell, P., and Wittenberg, C. (2008) DNA replication checkpoint promotes G 1-S transcription by inactivating the MBF repressor Nrm1. Proc. Natl. Acad. Sci. USA, 105, 11230-11235.
106. de Bruin, R.A. and Wittenberg, C. (2009) All eukaryotes: before turning off G 1-S transcription, please check your DNA. Cell Cycle, 8, 214-217.
107. Guo, C., Kosarek-Stancel, J.N., Tang, T.S., and Friedberg, E.C. (2009) Y-family DNA polymerases in mammalian cells. Cell Mol. Life Sci., 66, 2363-2381.
108. Schneider, R. and Grosschedl, R. (2007) Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev., 21, 3027-3043.
109. Rooney, J.P., George, A.D., Patil, A., Begley, U., Bessette, E., Zappala, M.R., Huang, X., Conklin, D.S., Cunningham, R.P., and Begley, T.J. (2009) Systems based mapping demonstrates that recovery from alkylation damage requires DNA repair, RNA processing, and translation associated networks. Genomics, 93, 42-51.