N-METHYL-N'-NITRO-N-NITROSOGUANIDINE INDUCED DNA-SEQUENCE ALTERATION - NONRANDOM COMPONENTS IN ALKYLATION MUTAGENESIS

被引:25
作者
GORDON, AJE
BURNS, PA
GLICKMAN, BW
机构
[1] Department of Biology, York University, Toronto, Ont. M3J 1P3
来源
MUTATION RESEARCH | 1990年 / 233卷 / 1-2期
基金
加拿大自然科学与工程研究理事会;
关键词
Alkylation mutagenesis; DNA sequence alteration; Escherichia coli lacI[!sup]-d[!/sup; Mutational specificity; N-Methyl-N′-nitro-N-nitrosoguanidine; Non-random mutant distribution;
D O I
10.1016/0027-5107(90)90154-V
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Our approach to the study of how the molecular nature of DNA modulates the behavior of mutational sites involves the characterisation of distributions of mutations. The Escherichia coli lacI genetic/M13 cloning system allows the comparison of base substitution frequencies at a large number of sites. The observed distribution of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced G:C → A:T transition (the predominant event), and A:T → G:C transition (a relatively rare event), is strikingly non-random. Some sites of G:C → A:T mutation are almost 100 times more often mutated by MNNG than the least susceptible sites. Sites of mutation, however, do not display a continuum of mutability, but rather can be strictly demarcated by their 5′ flanking base. Sites with a high frequency of occurrence share a common sequence motif, namely 5′-R-G-N-3′, which is the sole apparent feature that distinguishes them from sites less commonly mutated (i.e. 5′-Y-G-N-3′). A corollary of this defined site specificity is the absence of a strand bias in MNNG-induced lacI-d mutation. The availability of specific or non-specific alkylation-repair systems does not appear to alter the distribution of mutation, which suggests that the observed mutational distribution is a direct reflection of the initial damage distribution. MNNG does not belong to that class of compounds typified by ultraviolet light or 4-nitroquinoline-N-oxide which exhibit both random and non-random components of mutagenesis. © 1990.
引用
收藏
页码:95 / 103
页数:9
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