INSTABILITY OF SIMPLE REPETITIVE DNA SEQUENCES IN YEAST

描述(改编自研究人员摘要)：所有真核生物 含有简单重复DNA的片断，其中单个碱基或一个 少量的碱基重复多次。重复区 往往是不稳定的，在大小上以 比观察到的“正常”非重复DNA序列要高得多。 使用在编码序列中插入重复DNA的质粒 在可选择的基因中，可以在酵母中检测到区段不稳定性， 酿酒酵母。拟议中的实验检验了一些 这种类型的遗传不稳定性的性质。第一，酵母的突变体 将对那些增加了不稳定程度的国家进行审查。本研究 应产生与脊髓束不稳定机制相关的证据。 第二，改变序列或长度的影响 将对重复的DNA片段进行检查。第三，将确定 束长度的改变是否与交叉有关。 第四，转基因小鼠体内的简单不稳定性 将开发可监测的中继器。第五，搜索将是 为在酵母中大量扩增简单重复序列的机制而制造 细胞，因为到目前为止检测到的大多数变化都是小的 改变。

DESCRIPTION (adapted from investigator's abstract): All eukaryotes contain tracts of simple repetitive DNA, in which a single base or a small number of bases is repeated multiple times. Repetitive tracts tend to be unstable, increasing or decreasing in size at a rate that is much higher than that observed for "normal" non-repeated DNA sequences. Using plasmids with insertions of repetitive DNA in the coding sequence of selectable genes, tract instability can be assayed in the yeast, Saccharomyces cerevisiae. The proposed experiments examine some properties of this type of genetic instability. First, mutants of yeast that have increased levels of instability will be examined. This study should yield evidence relevant to the mechanisms of tract instability. Second, the effects of altering the sequence or the length of the repetitive DNA tracts will be examined. Third, it will be determined whether alterations in tract length are associated with crossing-over. Fourth, a transgenic mouse in which the in vivo instability of simple repeats can be monitored will be developed. Fifth, a search will be made for mechanisms allowing large expansions of simple repeats in yeast cells since most of the alterations detected to date represent small changes.