O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine.
1986; Elsevier BV; Volume: 261; Issue: 21 Linguagem: Inglês
10.1016/s0021-9258(18)67598-2
ISSN1083-351X
AutoresMichael D. Topal, J. Eadie, Michael N. Conrad,
Tópico(s)DNA and Nucleic Acid Chemistry
ResumoMutations were induced in the ampicillinase gene of a bacteriophage flJpBR322 chimera both by incorporation of OB-methyl-dGTP opposite T during DNA replication in vitro and by site-directed mutagenesis using 0%-methylguanine-containing oligonucleotides.After passage of the DNA through Escherichia coli, analysis of 151 Os-methyl-dGTP-induced mutations indicated a significantly greater number of unmutated mutation sites than expected, whereas the mutated sites generally fit a Poisson distribution.The unmutated sites are assumed to be caused by the inability of some sequences to tolerate the presence of a tetrahedral methyl group within the confines of a Watson-Crick helix (Toorchen, D., and Topal, M. D. (1983) Carcinogenesis 4, 1591-1597).A consensus of the DNA sequences surrounding unmutated mutation sites was derived.The consensus sequence had significant similarity to the region of the rat Harvey ras oncogene containing the N-methyl-Nnitrosourea activated site for transformation (Zarbl, H., Sukumar, S., Arthur, A. V., Dionisio, M.-Z., and Barbacid, M. (1985) Nature 315, 382-385).We propose that direct alkylation at OB of a guanine present within the consensus sequence may produce a DNA conformation less subject to repair.Mutation by OBmethylguanine-containing oligonucleotides demonstrated that repair of the OB-methylguanine lesions varied at least 3-4-fold with position of the lesion.
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