Department of Radiation Oncology, University of Virginia, Charlottesville, VA 22903, USA.
Int J Mol Sci. 2022 Oct 26;23(21):12937. doi: 10.3390/ijms232112937.
Microhomology-mediated end joining (MMEJ) is a highly mutagenic pathway to repair double-strand breaks (DSBs). MMEJ was thought to be a backup pathway of homologous recombination (HR) and canonical nonhomologous end joining (C-NHEJ). However, it attracts more attention in cancer research due to its special function of microhomology in many different aspects of cancer. In particular, it is initiated with DNA end resection and upregulated in homologous recombination-deficient cancers. In this review, I summarize the following: (1) the recent findings and contributions of MMEJ to genome instability, including phenotypes relevant to MMEJ; (2) the interaction between MMEJ and other DNA repair pathways; (3) the proposed mechanistic model of MMEJ in DNA DSB repair and a new connection with microhomology-mediated break-induced replication (MMBIR); and (4) the potential clinical application by targeting MMEJ based on synthetic lethality for cancer therapy.
微同源介导的末端连接（MMEJ）是一种修复双链断裂（DSBs）的高度突变途径。MMEJ 被认为是同源重组（HR）和经典非同源末端连接（C-NHEJ）的备用途径。然而，由于其在癌症许多不同方面的微同源的特殊功能，它在癌症研究中引起了更多的关注。特别是，它是由 DNA 末端切除引发的，并在同源重组缺陷型癌症中上调。在这篇综述中，我总结了以下内容：（1）MMEJ 对基因组不稳定性的最新发现和贡献，包括与 MMEJ 相关的表型；（2）MMEJ 与其他 DNA 修复途径的相互作用；（3）MMEJ 在 DNA DSB 修复中的拟议机制模型，以及与微同源介导的断裂诱导复制（MMBIR）的新联系；以及（4）基于合成致死性针对 MMEJ 的潜在临床应用，用于癌症治疗。
