Mutational specificity of N-methyl-N-nitrosourea in the lacI gene of Escherichia coli

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Abstract
The mutational specificity of the carcinogenic alkylating agent N-methyl-N-nitrosourea (MNU) was investigated through the DNA sequence characterisation of 104 lacI-d mutations induced by this agent in the lacI gene of Escherichia coli. The vast majority (95%) of MNU-induced mutations were G:C .fwdarw. A:T transitions. An analysis of neighbouring base sequence revealed that this transition was almost 10 times more likely to occur if the mutated guanine residue was preceded (5'') by a purine (R) rather than a pyrimidine (Y); apart from this 5''-R-G-3'' influence no other site specificity of mutation was observed. This 5''-flanking base influence on mutability has also been observed in this system with other mechanistically similar alkylating agents.