Maleki S, Cederberg H, Rannug U
Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
Mol Gen Genet. 1997 Mar 18;254(1):37-42. doi: 10.1007/s004380050388.
MS1 is one of the most variable minisatellites so far isolated from the human genome. We have previously reported an MS1 length-mutant frequency of 29.6% in overnight cultures of haploid yeast cells carrying a 1.35 kb MS1 allele. Here we present data on the instability of alleles with lengths ranging from 0.15 kb to 2.05 kb, which revealed a threshold of 0.75 kb, at and below which MS1 alleles were entirely stable. Larger alleles exhibited a length-related increase in mutation frequency. Chromosomal integration of various MS1 alleles, isolated from bacterial transformants, in haploid yeast cells also revealed a threshold for the onset of instability and a higher degree of mutability for longer alleles. DNA sequencing of alleles showed that the length changes were due to mutational events involving repeat units in the central region of MS1 which is composed of two variant repeat units only. The similarity between MS1 mutations in yeast and humans argues that yeast represents a suitable model organism for mechanistic studies on mutations occurring in human minisatellites.
MS1是迄今为止从人类基因组中分离出的最具变异性的小卫星之一。我们之前报道过，携带1.35 kb MS1等位基因的单倍体酵母细胞过夜培养物中，MS1长度突变频率为29.6%。在此，我们展示了长度范围从0.15 kb到2.05 kb的等位基因不稳定性的数据，这些数据揭示了一个0.75 kb的阈值，在该阈值及以下，MS1等位基因完全稳定。较大的等位基因表现出与长度相关的突变频率增加。从细菌转化体中分离出的各种MS1等位基因在单倍体酵母细胞中的染色体整合也揭示了不稳定性开始的阈值以及较长等位基因更高程度的可变性。等位基因的DNA测序表明，长度变化是由于涉及MS1中心区域重复单元的突变事件引起的，该区域仅由两个可变重复单元组成。酵母和人类中MS1突变的相似性表明，酵母是研究人类小卫星中发生的突变机制的合适模式生物。
