Freudenreich C H, Kantrow S M, Zakian V A
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Science. 1998 Feb 6;279(5352):853-6. doi: 10.1126/science.279.5352.853.
Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.
DNA三核苷酸重复序列（TNRs）的扩增是越来越多人类遗传疾病中的致病突变。在酿酒酵母中获得了CTG序列的大量扩增，并通过遗传和物理分析表明其是染色体断裂的长度依赖性位点。编码参与冈崎片段加工的核酸酶的RAD27的缺失导致CTG序列的长度依赖性不稳定以及扩增频率的大幅增加。本文所述的遗传分析可用于评估其他诱导人类TNR扩增或染色体脆性的因素。
