Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality
نویسندگان
چکیده
منابع مشابه
Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators.
Searching for a novel family of inactivators of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds...
متن کاملExpression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells.
DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated with their transferase activity levels, whereas Mer- cells contained undetecta...
متن کاملNovel synthesis of O-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O-methylguanine DNA methyltransferase (MGMT)
The human DNA repair protein O-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical importance. We describe a post-DNA synthesis s...
متن کاملNovel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT)
The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical importance. We describe a post-DNA synthesis...
متن کاملTumor O-methylguanine-DNA Methyltransferase Inactivation by Oral Lomeguatrib
Authors' A University Manches 3Neurosug NHS Trus Developme Urology, N
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ژورنال
عنوان ژورنال: Molecular Carcinogenesis
سال: 2012
ISSN: 0899-1987
DOI: 10.1002/mc.21964