Biological properties of imidazole ring-opened N7-methylguanine in M13mp18 phage DNA

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Biological properties of imidazole ring-opened N7-methylguanine in M13mp18 phage DNA.

Guanine residues methylated at the N-7 position (7-MeGua) are susceptible to cleavage of the imidazole ring yielding 2,6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine (Fapy-7-MeGua). The presence of Fapy-7-MeGua in DNA template causes stops in DNA synthesis in vitro by E. coli DNA polymerase I. The biological consequences of Fapy-7-MeGua lesions for survival and mutagenesis were investigated ...

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Imidazole ring-opened DNA purines and their biological significance.

Fragmentation of purine imidazole ring and production of formamidopyrimidines in deoxynucleosides (Fapy lesions) occurs upon DNA oxidation as well as upon spontaneous or alkali-triggered rearrangement of certain alkylated bases. Many chemotherapeutic agents such as cyclophosphamide or thiotepa produce such lesions in DNA. Unsubstituted FapyA and FapyG, formed upon DNA oxidation cause moderate i...

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Ring-opened 7-methylguanine residues in DNA are a block to in vitro DNA synthesis

Single-stranded M13mp18 phage DNA was methylated with dimethylsulfate (DMS), and further treated with alkali to ring-open N7-methylguanine residues and yield 2-6-diamino-4-hydroxy-5N-methylformamidopyrimidine (Fapy) residues. Nucleotide incorporation during in vitro DNA synthesis on methylated template using E. coli DNA polymerase Klenow fragment (Kf polymerase) was reduced compared to the unme...

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Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone.

DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a convention...

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Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium.

Schistosoma haematobium-infected patients are more likely to develop bladder cancer and be more exposed to carcinogenic N-nitroso compounds than uninfected patients. As N7-methylguanine is a marker of exposure to methylating agents of this type, we have measured N7-methyldeoxyguanosine 3'-monophosphate (N7-MedGp) by (32)P postlabeling. DNA was isolated from 42 paired normal and tumor tissue of ...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 1992

ISSN: 0305-1048,1362-4962

DOI: 10.1093/nar/20.12.3079