O6-methylguanine-DNA methyltransferase (MGMT): Can function explain a suicidal mechanism?

Medical Hypotheses

Volumn 77, Issue 5, 2011, Pages 857-860

  Gouws, Chrisna ^a   Pretorius, Pieter J ^a  

^a NORTH WEST UNIVERSITY   (South Africa)

Author keywords

[No Author keywords available]

Indexed keywords

METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE;

ARTICLE; CPG ISLAND; DNA ALKYLATION; DNA METHYLATION; DNA REPLICATION; ENZYME ACTIVITY; ENZYME MECHANISM; EXCISION REPAIR; GENE DELETION; GENE EXPRESSION; GENE MUTATION; HUMAN; MISMATCH REPAIR; NONHUMAN; PROMOTER REGION; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN FUNCTION; TRANSCRIPTION REGULATION; UBIQUITINATION;

CELL DEATH; ENZYME INDUCTION; HUMANS; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE;

EID: 80053950901     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2011.07.055     Document Type: Article

References (32)

1. Doak S.H., Brüsehafer K., Dudley E., et al. No-observed effect levels are associated with up-regulation of MGMT following MMS exposure. Mutat Res 2008, 648:9-14.
2. Zhong Y., Huang Y., Huang Y., et al. Effects of O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms on cancer: a meta-analysis. Mutagenesis 2010, 25:83-95.
3. Jacinto F.V., Esteller M. MGMT hypermethylation: a prognostic foe, a predictive friend. DNA Repair 2007, 6:1155-1160.
4. Liu L., Gerson S.L. Targeted modulation of MGMT: clinical implications. Clin Cancer Res 2006, 12:328-331.
5. Kaina B., Christmann M., Naumann S., Roos W.P. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair 2007, 6:1079-1099.
6. Kaina B. Critical steps in alkylation-induced aberration formation. Mutat Res 1998, 404:119-124.
7. Major G.N., Collier J.J. Repair of DNA lesion O6-methylguanine in hepatocellular carcinogenesis. J Hepatobiliary Pancreat Surg 1998, 5:355-366.
8. Grady W.M., Ulrich C.M. DNA alkylation and DNA methylation: cooperating mechanisms driving the formation of colorectal adenomas and adenocarcinomas?. Gut 2007, 56:318-320.
9. Margison G.P., Povey A.C., Kaina B., Santibanez Koref M.F. Variability and regulation of O6-alkylguanine-DNA alkyltransferase. Carcinogenesis 2003, 24:625-635.
10. Pegg A.E. Repair of O6-alkylguanine by alkyltransferases. Mutat Res 2000, 462:83-100.
11. Pieper R.O. Understanding and manipulating O6-methylguanine-DNA methyltransferase expression. Pharmacol Therapeut 1997, 74:285-297.
12. Lindahl T., Demple B., Robins P. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J 1982, 1:1359-1363.
13. Sedgwick B., Bates P.A., Paik J., Jacobs S.C., Lindahl T. Repair of alkylated DNA: recent advances. DNA Repair 2007, 6:429-442.
14. Srivenugopal K.S., Yuan X.-H., Friedman H.S., Ali-Osman F. Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1, 3-Bis(2-chloroethyl)-1-nitrosourea. Biochemistry 1996, 35:1328-1334.
15. Souliotis V.L., Sfikakis P.P., Anderson L.M., Kyrtopoulos S.A. Intra- and intercellular variations in the repair efficiency of O6-methylguanine, and their contribution to kinetic complexity. Mutat Res 2004, 568:155-170.
16. Thomale J., Seilerj F., Muller M.R., Seeber S., Rajewsky M.F. Repair of O6-alkylguanines in the nuclear DNA of human lymphocytes and leukaemic cells: analysis at the single-cell level. Brit J Cancer 1994, 69:698-705.
17. Baumann S., Keller G., Pühringer F., et al. The prognostic impact of O6-methylguanine-DNA methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma. Int J Cancer 2006, 119:264-268.
18. Esteller M., Risques R.-A., Toyota M., et al. Promoter hypermethylation of the DNA repair gene O6-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. Cancer Res 2001, 61:4689-4692.
19. Yin D., Xie D., Hofmann W.-K., et al. DNA repair gene O6-methylguanine-DNA methyltransferase: Promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors. Mol Carcinogen 2003, 36:23-31.
20. Bearzatto A., Szadkowski M., Macpherson P., Jiricny J., Karran P. Epigenetic regulation of the MGMT and hMSH6 DNA repair genes in cells resistant to methylating agents. Cancer Res 2000, 60:3262-3270.
21. Margison G.P., Santibáñez-Koref M.F. O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. BioEssays 2002, 24:255-266.
22. Shrivastav N., Li D., Essigmann J.M. Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation. Carcinogenesis 2010, 31:59-70.
23. Grombacher T., Mitra S., Kaina B. Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes. Carcinogenesis 1996, 17:2329-2336.
24. Sharma S., Salehi F., Scheithauer Bw, Rotondo F., Syro L.V., Kovacs K. Role of MGMT in tumor development, progression, diagnosis, treatment and prognosis. Anticancer Res 2009, 29:3759-3768.
25. Palmer T. Enzymes: biochemistry, biotechnology, clinical chemistry. Horwood Publishing Limited. 2001, pp. 402.
26. Pegg A.E. Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res 1990, 50:6119-6129.
27. Müller L., Gocke E., Lavé T., Pfister T. Ethyl methanesulfonate toxicity in Viracept-a comprehensive human risk assessment based on threshold data for genotoxicity. Toxicol Lett 2009, 190:317-329.
28. Drabløs F., Feyzi E., Aas P.A., et al. Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair 2004, 3:1389-1407.
29. Kryston T.B., Georgiev A.B., Pissis P., Georgakilas A.G. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 2011, 711:193-201.
30. Go Y.-M., Jones D.P. Redox control systems in the nucleus: mechanisms and functions. Antiox Redox Signal 2010, 13:489-509.
31. Pegg A.E., Fang Q., Loktionova N.A. Human variants of O6-alkylguanine-DNA alkyltransferase. DNA Repair 2007, 6:1071-1078.
32. Teo A.K.C., Oh H.K., Ali R.B., Li B.F.L. The modified human DNA repair enzyme O6-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. Mol Cell Biol 2001, 21:7105-7114.