Transversion-specific purine analogue mutagens and the mechanism of hydroxylaminopurine mutagenesis.
The tryptophan synthetase gene A series of mutants in E. coli has been used to examine the mutational specificity of over 80 purine base analogues. 4 purine analogues have been discovered that solely cause transversions. Evidence is presented that hydroxylaminopurine mutagenesis is caused by a covalent reaction of these compounds with DNA. The transversion-causing purine analogues are derivatives of 2-aminopurine (2AP) and 2,6-diaminopurine (2,6DAP). They stimulate the full reversion frequency of those trp A which can revert through an AT----CG transversion. 8 purine base analogues have been found that induce the AT----CG transversion at the trp A88 site; and 2-amino-6-methylaminopurine (2A6MAP) stimulates by 124-fold, 2-amino-6-ethylaminopurine by 20-fold, 2-methylaminopurine (2MAP) by 9.4-fold, 2,6-bismethylaminopurine by 25-fold, 2AP by 230-fold, 2,6DAP by 15-fold, 2.6-diaminopurine riboside by 5-fold, and 2-hydroxylaminopurine by 11-fold. The last 4 analogues also cause transitions. 2A6MAP, 2-amino-6-ethylaminopurine and 2,6-bismethylaminopurine stimulate only the AT----CG transversion while 2MAP additionally gives rise to AT----TA transversions. By testing other negative 2AP derivatives, the structural requirements necessary for AT----CG transversion mutagenesis have been determined. All 12 hydroxylaminopurine base analogues tested, 2,6-dimethoxyaminopurine and 2-hydrazinopurine were found to cause transition mutations. All of the compounds stimulated the AT----GC transition (by up to 1000-fold) and 11 of the 14 base analogues raised the GT----AT transition (by up to 450-fold). On increasing the hydroxylaminopurine concentration, the mutation frequency also increased concomitantly. Since 6-hydroxylamino-9-methylpurine and 6-methylhydroxylaminopurine cause transitions, the mechanism of hydroxylaminopurine mutagenesis cannot be entirely due to an alteration in tautomeric equilibria or "wobble" type base mispairing. It is proposed that a major mechanism for hydroxylaminopurine mutagenesis is due to the reaction of these compounds with the O6-position of guanine and the O4-position of thymine.[1]References
- Transversion-specific purine analogue mutagens and the mechanism of hydroxylaminopurine mutagenesis. Murray, V. Mutat. Res. (1987) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
