He Q, Cederberg H, Armour J A, May C A, Rannug U
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, S-106 91, Stockholm, Sweden.
Gene. 1999 May 31;232(2):143-53. doi: 10.1016/s0378-1119(99)00133-x.
Tandemly repeated DNA is a major component of the human genome, and includes loci contributing to human disease. Minisatellites include the most variable human loci described to date, and the mechanisms by which this variation is generated in humans have been studied in detail. Integration of human minisatellites into yeast not only provides a model for further dissecting the molecular basis of length change mutation at these loci, but also more generally allows the study of complex recombinational events in yeast. We have used human minisatellite MS205 integrated into yeast to study the structural details of length change mutations. Apart from showing that mutation at this locus in yeast has features similar to those observed at some minisatellites in humans, including meiosis-specificity, and polarity, in which exchange events are localised to one extremity of the array, we here, for the first time, directly demonstrate that a flanking element in yeast regulates the mutation process. The results therefore support the hypothesis that flanking initiators are involved in minisatellite mutation in humans. Furthermore, mutant alleles showed more complex rearrangements in one orientation than the other. The data also suggest that the mutational pathway for deletions might be different from the pathway generating inter-allelic exchanges and duplications.
串联重复DNA是人类基因组的主要组成部分，包括导致人类疾病的基因座。微卫星包含了迄今为止所描述的人类中变化最大的基因座，并且已经对人类中产生这种变异的机制进行了详细研究。将人类微卫星整合到酵母中，不仅为进一步剖析这些基因座长度变化突变的分子基础提供了一个模型，而且更广泛地允许对酵母中的复杂重组事件进行研究。我们利用整合到酵母中的人类微卫星MS205来研究长度变化突变的结构细节。除了表明酵母中该基因座的突变具有与人类某些微卫星中观察到的特征相似的特征，包括减数分裂特异性和极性（其中交换事件定位于阵列的一个末端）之外，我们在此首次直接证明酵母中的一个侧翼元件调节突变过程。因此，结果支持了侧翼引发剂参与人类微卫星突变的假说。此外，突变等位基因在一个方向上显示出比另一个方向更复杂的重排。数据还表明，缺失的突变途径可能与产生等位基因间交换和重复的途径不同。
