Center for Genomics and Systems Biology, New York University, New York 10003, USA.
Department of Biology, New York University, New York 10003, USA.
G3 (Bethesda). 2023 Mar 9;13(3). doi: 10.1093/g3journal/jkac330.
Mutations in simple sequence repeat loci underlie many inherited disorders in humans, and are increasingly recognized as important determinants of natural phenotypic variation. In eukaryotes, mutations in these sequences are primarily repaired by the MutSβ mismatch repair complex. To better understand the role of this complex in mismatch repair and the determinants of simple sequence repeat mutation predisposition, we performed mutation accumulation in yeast strains with abrogated MutSβ function. We demonstrate that mutations in simple sequence repeat loci in the absence of mismatch repair are primarily deletions. We also show that mutations accumulate at drastically different rates in short (<8 bp) and longer repeat loci. These data lend support to a model in which the mismatch repair complex is responsible for repair primarily in longer simple sequence repeats.
简单重复序列位点的突变是人类许多遗传性疾病的基础，并且越来越被认为是自然表型变异的重要决定因素。在真核生物中，这些序列的突变主要由 MutSβ 错配修复复合物修复。为了更好地理解该复合物在错配修复中的作用和简单重复序列突变易感性的决定因素，我们在缺失 MutSβ 功能的酵母菌株中进行了突变积累实验。我们证明，在没有错配修复的情况下，简单重复序列位点的突变主要是缺失。我们还表明，在较短（<8bp）和较长重复序列位点，突变以截然不同的速率积累。这些数据支持这样一种模型，即错配修复复合物主要负责修复较长的简单重复序列。
