CRISPR-Cas9 介导的基因组编辑中的 DNA 修复途径选择。
DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing.
机构信息
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
出版信息
Trends Genet. 2021 Jul;37(7):639-656. doi: 10.1016/j.tig.2021.02.008. Epub 2021 Apr 22.
Many clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-based genome editing technologies take advantage of Cas nucleases to induce DNA double-strand breaks (DSBs) at desired locations within a genome. Further processing of the DSBs by the cellular DSB repair machinery is then necessary to introduce desired mutations, sequence insertions, or gene deletions. Thus, the accuracy and efficiency of genome editing are influenced by the cellular DSB repair pathways. DSBs are themselves highly genotoxic lesions and as such cells have evolved multiple mechanisms for their repair. These repair pathways include homologous recombination (HR), classical nonhomologous end joining (cNHEJ), microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA). In this review, we briefly highlight CRISPR-Cas9 and then describe the mechanisms of DSB repair. Finally, we summarize recent findings of factors that can influence the choice of DNA repair pathway in response to Cas9-induced DSBs.
许多基于成簇规律间隔短回文重复序列（CRISPR）-CRISPR 相关蛋白 9（Cas9）的基因组编辑技术利用 Cas 核酸酶在基因组中的所需位置诱导 DNA 双链断裂（DSB）。随后，细胞 DSB 修复机制进一步处理 DSB，以引入所需的突变、序列插入或基因缺失。因此，基因组编辑的准确性和效率受细胞 DSB 修复途径的影响。DSB 本身是高度遗传毒性损伤，因此细胞已经进化出多种修复它们的机制。这些修复途径包括同源重组（HR）、经典非同源末端连接（cNHEJ）、微同源介导的末端连接（MMEJ）和单链退火（SSA）。在这篇综述中，我们简要介绍了 CRISPR-Cas9，然后描述了 DSB 修复的机制。最后，我们总结了最近发现的影响 Cas9 诱导的 DSB 后 DNA 修复途径选择的因素。
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