Department of Chemistry and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Physics, North Carolina State University, Raleigh, NC 27695, USA.
Curr Opin Struct Biol. 2024 Dec;89:102917. doi: 10.1016/j.sbi.2024.102917. Epub 2024 Sep 10.
DNA mismatch repair (MMR) requires coordinated sequential actions of multiple proteins during a window of time after the replication apparatus makes an error and before the newly synthesized DNA undergoes chromosome compaction and/or methylation of dGATC sites in some γ-proteobacteria. In this review, we focus on the steps carried out by MutS and MutL homologs that initiate repair. We connect new structural data to early and recent single-molecule FRET and atomic force microscopy (AFM) studies to reveal insights into how signaling within the MMR cascade connects MutS homolog recognition of a mismatch to downstream repair. We present unified models of MMR initiation that account for the differences in the strand discrimination signals between methyl- and non-methyl-directed MMR.
DNA 错配修复 (MMR) 需要在复制装置出错后到新合成的 DNA 经历染色体压缩和/或某些γ-变形菌中 dGATC 位点的甲基化之前的时间窗口内，多个蛋白质协调地进行连续的作用。在这篇综述中，我们专注于启动修复的 MutS 和 MutL 同源物所进行的步骤。我们将新的结构数据与早期和最近的单分子荧光共振能量转移和原子力显微镜 (AFM) 研究联系起来，以揭示 MMR 级联中的信号如何将 MutS 同源物对错配的识别与下游修复联系起来。我们提出了 MMR 起始的统一模型，该模型解释了甲基化和非甲基化指导的 MMR 之间链区分信号的差异。
