DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy

DNA Repair

Volumn 6, Issue 8, 2007, Pages 1100-1115

  Tubbs, Julie L ^a   Pegg, Anthony E ^b   Tainer, John A ^a,c  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

^c LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

Author keywords

AGT; DNA repair; MGMT; O6 Alkylguanine DNA alkyltransferase; O6 Methylguanine DNA methyltransferase; Protein crystal structure

Indexed keywords

1 N, 6 O ETHANOXANTHOSINE; 4 N P XYLYLENEDIAMINECYTOSINE; 4 O METHYLTHYMINE; 6 O ALKYLGUANINE DNA ALKYLTRANSFERASE; 6 O BENZYLGUANINE; 6 O METHYLGUANINE; ARGININE; CYSTEINE; CYTOSINE DERIVATIVE; DACARBAZINE; GUANINE; HELIX LOOP HELIX PROTEIN; PROCARBAZINE; STREPTAVIDIN; STREPTOZOCIN; TEMOZOLOMIDE; THYMINE; UNCLASSIFIED DRUG; XANTHOSINE;

APOPTOSIS; ARTICLE; BRAIN TUMOR; CANCER CHEMOTHERAPY; CANCER PREVENTION; CRYSTAL STRUCTURE; DNA ALKYLATION; DNA BINDING; DNA CROSS LINKING; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; DNA REPLICATION; DNA STRAND; DNA TRANSCRIPTION; GLIOBLASTOMA; HODGKIN DISEASE; HUMAN; HYDROGEN BOND; IN VITRO STUDY; LYMPHOMA; MELANOMA; METHANOCOCCUS JANNASCHII; MISMATCH REPAIR; NONHUMAN; PRIORITY JOURNAL; PYROCOCCUS; TUMOR CELL; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DNA; DNA MODIFICATION METHYLASES; DNA REPAIR; DNA REPAIR ENZYMES; DRUG RESISTANCE, NEOPLASM; HELIX-TURN-HELIX MOTIFS; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NEOPLASMS; NUCLEOTIDES; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; SEQUENCE HOMOLOGY, AMINO ACID; SUBSTRATE SPECIFICITY; TUMOR SUPPRESSOR PROTEINS;

EID: 34447323281     PISSN: 15687864     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dnarep.2007.03.011     Document Type: Article

References (150)

1. Rydberg B., and Lindahl T. Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-l-methionine is a potentially mutagenic reaction. EMBO J. 1 (1982) 211-216
2. Beranek D.T. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat. Res. 231 (1990) 11-30
3. Colvin D.M. Alkylating agents and platinum antitumor compounds. In: Frei H.J.F.E., Bast Jr. R.C., Kufe D.W., Morton D.L., and Weichselbaum R.R. (Eds). Cancer Medicine (1997), Willams & Wilkins, Media, PA 949-975
4. Kyrtopoulos S.A., Anderson L.M., Chhabra S.K., Souliotis V.L., Pletsa V., Valavanis C., and Georgiadis P. DNA adducts and the mechanism of carcinogenesis and cytotoxicity of methylating agents of environmental and clinical significance. Cancer Detect. Pev. 21 (1997) 391-405
5. Sundheim O., Vagbo C.B., Bjoras M., Sousa M.M., Talstad V., Aas P.A., Drablos F., Krokan H.E., Tainer J.A., and Slupphaug G. Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J. 25 (2006) 3389-3397
6. Liu L., and Gerson S.L. Targeted modulation of MGMT: clinical implications. Clin. Cancer Res. 12 (2006) 328-331
7. 6-alkylguanine-DNA alkyltransferase. Biochemistry 44 (2005) 15396-15405
8. 6-methylguanine-DNA methyltransferase activity: analyses of three residues at or near the methyl acceptor site. Carcinogenesis 13 (1992) 837-843
9. 6-methylguanine-DNA methyltransferase activity revealed by saturation mutagenesis with negative and positive screening. Mol. Gen. Genet. 243 (1994) 379-389
10. 6-alkylguanine DNA alkyltransferase protein. Biochem. Biophys. Res. Commun. 187 (1992) 425-431
11. 6-benzylguanine. Cancer Res. 53 (1993) 4750-4753
12. 6-alkylguanine-DNA alkyltransferase. Mutat. Res. 363 (1996) 15-25
13. 6-benzylguanine. Biochemistry 34 (1995) 7113-7119
14. 6-alkylguanine-DNA alkyltransferase. Biochemistry 38 (1999) 6801-6806
15. 6-alkylguanine-DNA alkyltranferase. Biochemistry 37 (1998) 12489-12495
16. 6-methylguanine-DNA methyltransferase stability, activity and substrate specificity. Carcinogenesis 15 (1994) 1895-1902
17. 6-alkylguanine-DNA-alkyltransferase. Biochem. Biophys. Res. Commun. 199 (1994) 285-291
18. Daniels D.S., Mol C.D., Arvai A.S., Kanugula S., Pegg A.E., and Tainer J.A. Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding. EMBO J. 19 (2000) 1719-1730
19. 6-alkylguanine-DNA alkyltransferase in E. coli increases cell killing and mutations by N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis 20 (1999) 103-108
20. Samson L., Han S., Marquis J.C., and Rasmussen L.J. Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair. Carcinogenesis 18 (1997) 919-924
21. 4-methylthymine. Suggestive evidence for O4-methylthymine repair by eukaryotic methyltransferases. J. Biol. Chem. 266 (1991) 2767-2771
22. 6-alkylguanine-DNA alkyltransferase. Progr. Nucleic Acid Res. Mol. Biol. 51 (1995) 167-223
23. 6-alkylguanine-DNA alkyltransferases. J. Biol. Chem. 272 (1997) 8332-8339
24. 6-alkylguanine-DNA alkyltransferase. Chem. Res. Toxicol. 12 (1999) 127-131
25. 6-methylguanine DNA methyltransferase (MGMT). Nucleic Acids Res 34 (2006) 1884-1891
26. 6-alkylguanine-DNA alkyltransferase. J. Med. Chem. 47 (2004) 3887-3891
27. 6-alkylguanine-DNA alkyltransferase. J. Med. Chem. 37 (1994) 342-347
28. 6-alkylguanine-DNA alkyltransferase. J. Med. Chem. 38 (1995) 359-365
29. 6-(1-cyclopentenylmethyl)guanine. J. Med. Chem. 43 (2000) 4071-4083
30. 6-alkylguanine-DNA alkyltransferase. J. Med. Chem. 35 (1992) 4486-4491
31. 6-benzylguanine analogs in mice. Cancer Chemother. Pharmacol. 47 (2001) 63-69
32. 6-(hetarylmethyl)guanines having basic rings in the side chain. J. Med. Chem. 41 (1998) 5265-5271
33. 6-methylguanine-DNA methyltransferase (MGMT): synthesis, molecular modeling, and structure-activity relationships. J. Med. Chem. 44 (2001) 4050-4061
34. 6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors. Int. J. Cancer 93 (2001) 373-379
35. 6-fluorobenzylguanines on chloroethylnitrosourea cytotoxicity in tumor cells. Life Sci. 58 (1996) PL303-PL308
36. 6-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 28 (2000) 393-401
37. 6-methylguanine-DNA methyltransferase from E. coli. EMBO J. 13 (1994) 1495-1501
38. 6-methylguanine-DNA methyltransferase. J. Mol. Biol. 292 (1999) 707-716
39. Roberts A., Pelton J.G., and Wemmer D.E. Structural studies of MJ1529, an O(6)-methylguanine-DNA methyltransferase. Magn. Reson. Chem. 44 (2006) 71-82
40. 6-alkylguanine-DNA alkyltransferase. Mutat. Res. 460 (2000) 151-163
41. 6-alkylguanine-DNA alkyltransferase. Biochemistry 42 (2003) 980-990
42. Daniels D.S., Woo T.T., Luu K.X., Noll D.M., Clarke N.D., Pegg A.E., and Tainer J.A. DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat. Struct. Mol. Biol. 11 (2004) 714-720
43. Duguid E.M., Rice P.A., and He C. The structure of the human AGT protein bound to DNA and its implications for damage detection. J. Mol. Biol. 350 (2005) 657-666
44. Kanugula S., and Pegg A.E. Novel DNA repair alkyltransferase from Caenorhabditis elegans. Env. Mol. Mutagen. 38 (2001) 235-243
45. 6-alkylguanine-DNA alkyltransferase and endonuclease V activities. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 3617-3622
46. Verdemato P.E., Brannigan J.A., Damblon C., Zuccotto F., Moody P.C., and Lian L.Y. DNA-binding mechanism of the Escherichia coli Ada O(6)-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 28 (2000) 3710-3718
47. Hollis T., Ichikawa Y., and Ellenberger T. DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA. EMBO J. 19 (2000) 758-766
48. Barrett T.E., Savva R., Panayotou G., Barlow T., Brown T., Jiricny J., and Pearl L.H. Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions. Cell 92 (1998) 117-129
49. Lau A.Y., Scharer O.D., Samson L., Verdine G.L., and Ellenberger T. Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision. Cell 95 (1998) 249-258
50. Slupphaug G., Mol C.D., Kavli B., Arvai A.S., Krokan H.E., and Tainer J.A. A nucleotideflipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 384 (1996) 87-92
51. Bruner S.D., Norman D.P., and Verdine G.L. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403 (2000) 859-866
52. Mol C.D., Izumi T., Mitra S., and Tainer J.A. DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination. Nature 403 (2000) 451-456
53. Hosfield D.J., Guan Y., Haas B.J., Cunningham R.P., and Tainer J.A. Structure of the DNA repair enzyme endonuclease IV and its DNA complex: double-nucleotide flipping at abasic sites and three-metal-ion catalysis. Cell 98 (1999) 397-408
54. Parikh S.S., Mol C.D., Slupphaug G., Bharati S., Krokan H.E., and Tainer J.A. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 17 (1998) 5214-5226
55. a and high reactivity of cysteine 145. Biochemistry 42 (2003) 10965-10970
56. 6-alkylguanine-DNA alkyltransferase. Effects of protein and DNA alkylation on complex stability. J. Biol. Chem. 278 (2003) 7973-7980
57. 6-arylmethylguanines. Int. J. Cancer. 63 (1995) 148-151
58. 6-alkylguanine-DNA alkyltransferases. Chem. Biol. 10 (2003) 827-835
59. 6-alkylguanine-DNA alkyltransferase. J. Biol. Chem. 280 (2005) 30873-30881
60. Begley T.J., and Samson L.D. Reversing DNA damage with a directional bias. Nat. Struct. Mol. Biol. 11 (2004) 688-690
61. 6-methylguanine lesion. Mol. Cell. Biol. 18 (1998) 1660-1669
62. 6-benzylguanine or N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis 12 (1991) 1679-1683
63. 6-benzylguanine or 1,3-bis(2-chloroethyl)-1-nitrosourea. Biochemistry 35 (1996) 1328-1334
64. 6-alkylguanine-DNA alkyltransferase. Carcinogenesis 23 (2002) 823-830
65. 6-alkylguanine DNA alkyltransferase. Protein Sci. 13 (2004) 301-305
66. Teo A.K., Oh H.K., Ali R.B., and Li B.F. The modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. Mol. Cell. Biol. 21 (2001) 7105-7114
67. 6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms. Int. J. Mol. Med. 16 (2005) 553-557
68. 6-alkylguanine-DNA alkyltransferase. DNA Repair 6 (2007) 1071-1078
69. 6-benzylguanine. Biochem. Pharmacol. 58 (1999) 1279-1285
70. 6-Alkylguanine DNA lesions trigger apoptosis. Carcinogenesis 19 (1998) 369-372
71. Hickman M.J., and Samson L.D. Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 10764-10769
72. D'Atri S., Tentori L., Lacal P.M., Graziani G., Pagani E., Benincasa E., Zambruno G., Bonmassar E., and Jiricny J. Involvement of the mismatch repair system in temozolomide-induced apoptosis. Mol. Pharmacol. 54 (1998) 334-341
73. Roos W.P., and Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol. Med. 12 (2006) 440-450
74. Erickson L.C., Bradley M.O., Ducore J.M., Ewig R.A., and Kohn K.W. DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas. Proc. Natl. Acad. Sci. U.S.A. 77 (1980) 467-471
75. 6-alkylguanine-DNA alkyltransferase from human leukemic cells. Prevention of chloroethylnitrosourea-induced cross-links by purified enzyme. Pharmacol. Ther. 31 (1985) 121-140
76. Ludlum D.B. The chloroethylnitrosoureas: sensitivity and resistance to cancer chemotherapy at the molecular level. Cancer Invest. 15 (1997) 588-598
77. 1-bis(2-chloroethyl)-nitrosourea cross-links N1 of deoxyguanosine to N3 of deoxycytidine on opposite strands of duplex DNA. Cancer Res. 59 (1999) 4363-4368
78. Bodell W.J., Tokuda K., and Ludlum D.B. Differences in DNA alkylation products formed in sensitive and resistant human glioma cells treated with N-(2-chloroethyl)-N-nitrosourea. Cancer Res. 48 (1988) 4489-4492
79. Belanich M., Pastor M., Randall T., Guerra D., Kibitel J., Alas L., Li B., Citron M., Wasserman P., White A., Eyre H., Jaeckle K., Schulman S., Rector D., Prados M., Coons S., Shapiro W., and Yarosh D. Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. 56 (1996) 783-788
80. 6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group Study. J. Clin. Oncol. 16 (1998) 3310-3315
81. 6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients. Can. J. Neurol. Sci. 26 (1999) 104-109
82. Kat A., Thilly W.G., Fang W.H., Longley M.J., Li G.M., and Modrich P. An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 6424-6428
83. Takagi Y., Takahashi M., Sanada M., Ito R., Yamaizumi M., and Sekiguchi M. Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis. DNA Repair 7 (2003) 1135-1146
84. Karran P. Mechanism of tolerance to DNA damaging therapeutic drugs. Carcinogenesis 22 (2001) 1931-1937
85. 6-methylguanine lesions in human nuclear extracts. J. Biol. Chem. 281 (2006) 22674-22683
86. Lin D.P., Wang Y., Scherer S.J., Clark A.B., Yang K., Avdievich E., Jin B., Werling U., Parris T., Kurihara N., Umar A., Kucherlapati R., Lipkin M., Kunkel T.A., and Edelmann W. An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Res. 64 (2004) 517-522
87. Yang G., Scherer S.J., Shell S.S., Yang K., Kim M., Lipkin M., Kucherlapati R., Kolodner R.D., and Edelmann W. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell 6 (2004) 139-150
88. 6-methylguanine adducts. Mol. Cell 22 (2006) 501-510
89. Newlands E.S., Stevens M.F., Wedge S.R., Wheelhouse R.T., and Brock C. Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treatment Rev. 23 (1997) 35-61
90. Friedman H.S., McLendon R.E., Dolan M.E., Pegg A.E., Moschel R.C., Colvin O.M., Cokgor I., Friedman A.H., Schold S.C., Bigner D.D., and Modrich P.L. The biology of sensitivity and resistance to the molecule (temozolomide). Proc. Am. Assoc. Cancer Res. 40 (1999) 754-755
91. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., Curschmann J., Janzer R.C., Ludwin S.K., Gorlia T., Allgeier A., Lacombe D., Cairncross J.G., Eisenhauer E., and Mirimanoff R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352 (2005) 987-996
92. Hegi M.E., Diserens A.C., Gorlia T., Hamou M.F., de Tribolet N., Weller M., Kros J.M., Hainfellner J.A., Mason W., Mariani L., Bromberg J.E., Hau P., Mirimanoff R.O., Cairncross J.G., Janzer R.C., and Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 352 (2005) 997-1003
93. 6-methylguanine DNA methyltransferase in human cancer. Oncogene 23 (2004) 1-8
94. 6-alkylguanine-DNA alkyltransferase as a target for cancer chemotherapy. In: Ehrlich E.M. (Ed). DNA Alterations in Cancer: Genetic and Epigenetic Changes (2000), Eaton Publishing, Natick, MA 471-488
95. 6-Alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. BioEssays 24 (2002) 255-266
96. Gerson S.L. MGMT: its role in cancer aetiology and cancer therapeutics. Nat. Rev. Cancer 4 (2004) 296-307
97. 6-methylguanine-DNA methyltransferase expression. Cancer Res. 53 (1993) 1731-1734
98. Zhang Q., Ohannesian D.W., and Erickson L.C. Hammerhead ribozyme-mediated sensitization of human tumor cells after treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. J. Pharmacol. Exp. Ther. 309 (2004) 506-514
99. Micetich K.C., Futscher B., Koch D., Fisher R.I., and Erickson L.C. Phase I study of streptozotocin- and carmustine-sequenced administration in patients with advanced cancer. J. Natl. Cancer Inst. 84 (1992) 256-260
100. Hammond L.A., Eckardt J.R., Kuhn J.G., Gerson S.L., Johnson T., Smith L., Drengler R.L., Campbell E., Weiss G.R., Von Hoff D.D., and Rowinsky E.K. A randomized phase I and pharmacological trial of sequences of 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide in patients with advanced solid neoplasms. Clin. Cancer Res. 10 (2004) 1645-1656
101. 6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 5368-5372
102. 6-benzylguanine. Biochemistry 32 (1993) 11998-12006
103. 6-Benzylguanine and its role in chemotherapy. Clin. Cancer Res. 3 (1997) 837-847
104. 6-benzylguanine metabolism. Biochem. Pharmacol. 61 (2001) 721-726
105. 6-benzylguanine in patients with surgically resectable tumors. Clin. Cancer Res. 8 (2002) 2519-2523
106. 6-benzylguanine. J. Clin. Pharmacol. 43 (2003) 881-893
107. 6-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma. J. Clin. Oncol. 2 (2002) 22277-22283
108. 6-Benzylguanine-mediated enhancement of chemotherapy. Mol. Cancer Ther. 1 (2002) 943-948
109. Dolan M.E. Inhibition of DNA repair as a means of increasing the antitumor activity of DNA reactive agents. Adv. Drug Deliv. Rev. 26 (1997) 105-118
110. 6-Benzylguanine in humans: metabolic, pharmacokinetic and pharmacodynamic findings. J. Clin. Oncol. 16 (1998) 1803-1810
111. 6-Benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair. Cancer Res. 59 (1999) 2402-2410
112. 6-benzylguanine and carmustine in patients with advanced soft tissue sarcoma. Cancer Chemother. Pharmacol. 58 (2006) 634-639
113. 6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma. Clin. Cancer Res. 11 (2005) 7861-7865
114. 6-Benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma. Cancer Res. 60 (2000) 6307-6310
115. 6-benzylguanine for patients with recurrent or progressive malignant glioma. J. Clin. Oncol. 23 (2005) 7178-7187
116. 6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors. J. Clin. Oncol. 23 (2005) 7646-7653
117. Middleton M.R., and Margison G.P. Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway. Lancet Oncol. 4 (2003) 37-44
118. 6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin. Cancer Res. 12 (2006) 1577-1584
119. 6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model. Int. J. Cancer 100 (2002) 615-617
120. 6-(4-Bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts. Br. J. Cancer. 93 (2005) 1152-1156
121. Woolford L.B., Southgate T.D., Margison G.P., Milsom M.D., and Fairbairn L.J. The P140K mutant of human O(6)-methylguanine-DNA-methyltransferase (MGMT) confers resistance in vitro and in vivo to temozolomide in combination with the novel MGMT inactivator O(6)-(4-bromothenyl)guanine. J. Gene Med. 8 (2006) 29-34
122. 6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide. Clin. Cancer Res. 7 (2001) 421-428
123. 6-alkylguanine-DNA alkyltransferase. Biochemistry 41 (2002) 8689-8697
124. 6-methylguanine-DNA methyltransferase (MGMT): synthesis, molecular modeling and structure-activity relationships. J. Med. Chem. 44 (2001) 4050-4061
125. 6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors. Int. J. Cancer 93 (2001) 373-379
126. Argiles J.M., and Lopez-Soriano F.J. Why do cancer cells have such a high glycolytic rate?. Med. Hypotheses 32 (1990) 151-155
127. Yamamoto T., Seino Y., Fukumoto H., Koh G., Yano H., Inagaki N., Yamada Y., Inoue K., Manabe T., and Imura H. Over-expression of facilitative glucose transporter genes in human cancer. Biochem. Biophys. Res. Commun. 170 (1990) 223-230
128. 6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors: comparison with nonconjugated inhibitors and effect on fotemustine and temozolomide-induced cell death. J. Pharmacol. Exp. Ther. 311 (2004) 585-593
129. 6-benzyl-2′-deoxyguanosine. J. Med. Chem. 48 (2005) 256-261
130. Leamon C.P., and Reddy J.A. Folate-targeted chemotherapy. Adv. Drug Deliv. Rev. 56 (2004) 1127-1141
131. Low P.S., and Antony A.C. Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv. Drug Deliv. Rev. 56 (2004) 1055-1058
132. 6-benzylguanine. Biochem. Pharmacol. 63 (2002) 1431-1442
133. 6-alkylguanine DNA alkyltransferases in human hematopoietic cells. Mol. Cancer Therap. 6 (2006) 121-129
134. 6-benzylguanine-resistant alkyltransferase mutations in mismatch-deficient colon cancer. Cancer Res. 62 (2002) 3070-3076
135. 6-alkylguanine-DNA alkyltransferase mutations. Mol. Cancer Ther. 3 (2004) 1127-1135
136. Milsom M.D., and Fairbairn L.J. Protection and selection for gene therapy in the hematopoietic system. J. Gene Med. 6 (2004) 133-146
137. 6-methylguanine-DNA-methyl transferase. J. Gene Med. 8 (2006) 972-979
138. 6-methylguanine DNA methyltransferase. Cancer Gene Ther. 13 (2006) 886-895
139. 6-methylguanine-DNA methyltransferase in hematopoietic cells. Mol. Ther. 13 (2006) 391-400
140. Zielske S.P., Reese J.S., Lingas K.T., Donze J.R., and Gerson S.L. In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning. J. Clin. Invest. 112 (2003) 1561-1570
141. Persons D.A., Allay E.R., Sawai N., Hargrove P.W., Brent T.P., Hanawa H., Nienhuis A.W., and Sorrentino B.P. Successful treatment of murine beta-thalassemia using in vivo selection of genetically modified, drug-resistant hematopoietic stem cells. Blood 102 (2003) 506-513
142. 6-benzylguanine and 1,3-bis-(2-chloroethyl)-1-nitrosourea. Mol. Cancer Ther. 2 (2003) 1321-1329
143. Richard E., Robert E., Cario-Andre M., Ged C., Geronimi F., Gerson S.L., de Verneuil H., and Moreau-Gaudry F. Hematopoietic stem cell gene therapy of murine protoporphyria by methylguanine-DNA-methyltransferase-mediated in vivo drug selection. Gene Ther. 11 (2004) 1638-1647
144. 6-benzylguanine and 1,3-bis(2-chloroethyl)-nitrosourea or temozolomide. Hum. Gene Ther. 15 (2004) 758-769
145. 6-methylguanine-DNA-methyltransferase and HOXB4. Mol. Ther. 10 (2004) 862-873
146. Hitomi K., Iwai S., and Tainer J.A. The intricate structural chemistry of base excision repair machinery: implications for DNA damage recognition, removal, and repair. DNA Repair 6 (2007) 410-428
147. Shin D.S., Chahwan C., Huffman J.L., and Tainer J.A. Structure and function of the double-strand break repair machinery. DNA Repair 3 (2004) 863-873
148. Huffman J.L., Sundheim O., and Tainer J.A. DNA base damage recognition and removal: new twists and grooves. Mutat. Res. 577 (2005) 55-76
149. S.E. Tsutakawa, G.L. Hura, K.A. Frankel, P.K. Cooper, J.A. Tainer, Structural analysis of flexible proteins in solution by small angle X-ray scattering combined with crystallography, J. Struct. Biol. (2006), in press.
150. J.J. Perry, L. Fan, J.A. Tainer, Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair, Neuroscience (2006), in press.