Department of Biology, Department of Radiation Oncology, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6153-8. doi: 10.1073/pnas.1115361109. Epub 2012 Apr 2.
Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.
错配修复 (MMR) 是一种主要的 DNA 修复途径，存在于生命各个分支的细胞中，它以链特异性的方式去除复制错误，从而优先从 DNA 的新复制链上去除错配的核苷酸。在这里，我们证明了 MMR 在帮助非分裂细胞产生新表型方面的作用。我们表明，在复制过程中逃避 MMR 的酵母错配可以以后以与复制链无关的方式在非分裂细胞中发生 MMR 活性，导致完全野生型或突变 DNA 序列。在一种情况下，这种活性负责似乎是适应性突变。这种与复制链无关的 MMR 活性可能有助于非分裂细胞中肿瘤的形成，也可能导致 Ig 基因体细胞高频突变中观察到的突变。
