DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing.

DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing.
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DOI:
10.1016/j.tig.2021.02.008
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发表时间:
2021-07
期刊:
Trends in genetics : TIG
影响因子:
--
通讯作者:
Greene EC
Greene EC
中科院分区:
其他
文献类型:
--
作者:
Xue C;Greene EC

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许多基于 CRISPR-Cas 的基因组编辑技术利用 Cas 核酸酶在基因组内的所需位置诱导 DNA 双链断裂 (DSB)。然后,需要通过细胞 DSB 修复机制对 DSB 进行进一步处理,以引入所需的突变、序列插入或基因删除。因此,基因组编辑的准确性和效率受到细胞 DSB 修复途径的影响。 DSB 本身就是高度基因毒性的病变,因此细胞已经进化出多种修复机制。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 系统,然后描述了 DSB 修复的机制。最后,我们总结了影响 Cas9 诱导 DSB 的 DNA 修复途径选择的因素的最新发现。
Many CRISPR-Cas-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 non-homologous end joining (cNHEJ), microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA). In this review, we briefly highlight the CRISPR-Cas9 system and we then describe the mechanisms of DSB repair. Finally, we summarize recent findings of factors that can influence the choice of DNA repair pathway response to Cas9-induced DSBs.
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