Department of Physics, Pohang University of Science & Technology (POSTECH), Pohang 37673, Korea.
Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
J Mol Biol. 2018 Oct 26;430(22):4469-4480. doi: 10.1016/j.jmb.2018.05.032. Epub 2018 May 21.
DNA mismatch repair (MMR) corrects DNA base-pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic molecular coordination of sequential downstream pathways. The temporal and mechanistic order of molecular events is essential to insure interactions in MMR that occur over long distances on the DNA. Biophysical real-time studies of highly conserved components on mismatched DNA have shed light on the mechanics of MMR. Single-molecule imaging has visualized stochastically coordinated MMR interactions that are based on thermal fluctuation-driven motions. In this review, we describe the role of diffusivity and stochasticity in MMR beginning with mismatch recognition through strand-specific excision. We conclude with a perspective of the possible research directions that should solve the remaining questions in MMR.
DNA 错配修复 (MMR) 纠正了 DNA 复制过程中发生的 DNA 碱基对错误。MMR 通过下游途径的动态分子协调，催化链特异性 DNA 降解和重新合成。分子事件的时间和机制顺序对于确保 DNA 上长距离发生的 MMR 相互作用至关重要。对高度保守的错配 DNA 成分的生物物理实时研究揭示了 MMR 的力学。单分子成像已经可视化了基于热波动驱动运动的随机协调的 MMR 相互作用。在这篇综述中，我们从错配识别开始，通过链特异性切除，描述了扩散性和随机性在 MMR 中的作用。最后，我们展望了可能的研究方向，这些方向应该能够解决 MMR 中剩余的问题。
