CHEMICAL CARCINOGENS AND FRAMESHIFT MUTATION IN YEAST

将在酿酒酵母中进行移码突变研究 使用基因和生物化学相结合的方法。来自多个来源的证据 表明原核生物中的框架移位发生在单调的碱基序列中(GGGG 或AAA)。我们的证据表明，酵母移码抑制子抑制了 四个基本码字GGGGG。我们将对突变的甘氨酸tRNA在我们的 抑制子菌株获得分子变化的直接证据 相框移位。此外，这一序列工作应该提供重要的证据 非孟德尔决定簇(PSI离子)对甘氨酸tRNA的影响。这个 甘氨酸移码抑制基因将通过常规和非整倍体进行定位 映射。第二类ICR可逆突变的抑制子(可能 Be CCCC)将进行生化和遗传分析。突变 提高这些移码突变的频率将被表征。一些人 其中一些可能会影响修复系统，另一些可能会影响诱变剂的渗透性。 酵母中两类新的潜在移码基因将被分离和 特色化的。我们将在自发的极地HIS4中寻找移帧 变种人。这些突变体的抑制子将被分离并将tRNAs 以双标记实验为特征。实验旨在揭示 ICR-170可逆性线粒体(MIT负)突变试图 描述线粒体遗传系统对 移码突变。最终，这些研究可能会导致 一株能够检测黄曲霉毒素基因移码突变的菌株的构建 细胞核和线粒体基因组中的致癌物。

Frameshift mutagenesis will be studied in the yeast Saccharomyces cerevisiae using a combined genetic and biochemical approach. Evidence from many sources suggests that frameshifts in procaryotes occur in monotonous runs of bases (GGGG or AAA). Our evidence suggests that yeast frameshift suppressors suppress the four base code word GGGG. We will sequence the mutant glycine tRNA in our suppressor strains to obtain direct evidence for the molecular change in the frameshifts. In addition this sequence work should provide important evidence on the effect of the non-Mendelian determinant (PSI ion) on glycine tRNA. The glycine frameshift suppressors will be mapped by conventional and aneuploid mapping. Suppressors of a second class of ICR revertible mutations (which could be CCCC) will be analyzed biochemically and genetically. Mutations which enhance the frequency of these frameshift mutations will be characterized. Some of these may affect repair systems and others the permeability of mutagens. Two new classes of potential frameshifts in yeast will be isolated and characterized. We will search for frameshifts among spontaneous polar his4 mutants. Suppressors of such mutants will be isolated and the tRNAs characterized by double label experiments. Experiments are designed to uncover ICR-170 revertible mitochondrial (MIT minus) mutations in an attempt to characterize the susceptibility of the mitochondrial genetic system to frameshift mutagenesis. Ultimately, these studies could lead to the construction of a strain capable of detecting frameshift mutations induced by carcinogens in both the nuclear and the mitochondrial genomes.