• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

通过操纵DNA修复机制来控制基因编辑。

Control of gene editing by manipulation of DNA repair mechanisms.

作者信息

Danner Eric, Bashir Sanum, Yumlu Saniye, Wurst Wolfgang, Wefers Benedikt, Kühn Ralf

机构信息

Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, 13125, Berlin, Germany.

Berlin Institute of Health, Kapelle-Ufer 2, 10117, Berlin, Germany.

出版信息

Mamm Genome. 2017 Aug;28(7-8):262-274. doi: 10.1007/s00335-017-9688-5. Epub 2017 Apr 3.

DOI:10.1007/s00335-017-9688-5
PMID:28374058
Abstract

DNA double-strand breaks (DSBs) are produced intentionally by RNA-guided nucleases to achieve genome editing through DSB repair. These breaks are repaired by one of two main repair pathways, classic non-homologous end joining (c-NHEJ) and homology-directed repair (HDR), the latter being restricted to the S/G2 phases of the cell cycle and notably less frequent. Precise genome editing applications rely on HDR, with the abundant c-NHEJ formed mutations presenting a barrier to achieving high rates of precise sequence modifications. Here, we give an overview of HDR- and c-NHEJ-mediated DSB repair in gene editing and summarize the current efforts to promote HDR over c-NHEJ.

摘要

DNA双链断裂(DSB)由RNA引导的核酸酶有意产生,以通过DSB修复实现基因组编辑。这些断裂通过两种主要修复途径之一进行修复,即经典非同源末端连接(c-NHEJ)和同源定向修复(HDR),后者仅限于细胞周期的S/G2期,且频率明显较低。精确的基因组编辑应用依赖于HDR,大量由c-NHEJ形成的突变对实现高比例的精确序列修饰构成了障碍。在这里,我们概述了基因编辑中HDR和c-NHEJ介导的DSB修复,并总结了目前促进HDR优于c-NHEJ的研究工作。

相似文献

1
Control of gene editing by manipulation of DNA repair mechanisms.通过操纵DNA修复机制来控制基因编辑。
Mamm Genome. 2017 Aug;28(7-8):262-274. doi: 10.1007/s00335-017-9688-5. Epub 2017 Apr 3.
2
Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks.促进同源定向修复选择的方法以应对 CRISPR/Cas9 诱导的双链断裂。
Int J Mol Sci. 2020 Sep 4;21(18):6461. doi: 10.3390/ijms21186461.
3
Opportunities and challenges with CRISPR-Cas mediated homologous recombination based precise editing in plants and animals.基于CRISPR-Cas介导的同源重组在动植物中进行精确编辑的机遇与挑战。
Plant Mol Biol. 2023 Jan;111(1-2):1-20. doi: 10.1007/s11103-022-01321-5. Epub 2022 Oct 31.
4
Highly efficient CRISPR/HDR-mediated knock-in for mouse embryonic stem cells and zygotes.用于小鼠胚胎干细胞和受精卵的高效CRISPR/HDR介导的基因敲入
Biotechniques. 2015 Oct 1;59(4):201-2, 204, 206-8. doi: 10.2144/000114339. eCollection 2015 Oct.
5
Enhancement of CRISPR-Cas9 induced precise gene editing by targeting histone H2A-K15 ubiquitination.通过靶向组蛋白 H2A-K15 泛素化增强 CRISPR-Cas9 诱导的精确基因编辑。
BMC Biotechnol. 2020 Oct 23;20(1):57. doi: 10.1186/s12896-020-00650-x.
6
Increasing CRISPR/Cas9-mediated homology-directed DNA repair by histone deacetylase inhibitors.组蛋白去乙酰化酶抑制剂增强 CRISPR/Cas9 介导的同源定向 DNA 修复。
Int J Biochem Cell Biol. 2020 Aug;125:105790. doi: 10.1016/j.biocel.2020.105790. Epub 2020 Jun 10.
7
Modulating DNA Repair Pathways to Improve Precision Genome Engineering.调控 DNA 修复途径以提高精确基因组工程。
ACS Chem Biol. 2018 Feb 16;13(2):389-396. doi: 10.1021/acschembio.7b00777. Epub 2017 Dec 20.
8
Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and cell type on genome-editing.对同源定向修复(HDR)和非同源末端连接(NHEJ)的系统定量揭示了基因座、核酸酶和细胞类型对基因组编辑的影响。
Sci Rep. 2016 Mar 31;6:23549. doi: 10.1038/srep23549.
9
Non-Homologous End Joining and Homology Directed DNA Repair Frequency of Double-Stranded Breaks Introduced by Genome Editing Reagents.基因组编辑试剂引入的双链断裂的非同源末端连接和同源定向DNA修复频率
PLoS One. 2017 Jan 17;12(1):e0169931. doi: 10.1371/journal.pone.0169931. eCollection 2017.
10
Ligation-assisted homologous recombination enables precise genome editing by deploying both MMEJ and HDR.连接辅助同源重组通过部署 MMEJ 和 HDR 实现精确的基因组编辑。
Nucleic Acids Res. 2022 Jun 24;50(11):e62. doi: 10.1093/nar/gkac118.

引用本文的文献

1
Refined DNA repair manipulation enables a universal knock-in strategy in mouse embryos.优化的DNA修复操作可实现小鼠胚胎中的通用敲入策略。
Nat Commun. 2025 Jul 15;16(1):6502. doi: 10.1038/s41467-025-61696-z.
2
Cloning-Free Targeting of Endogenous Loci to Generate Fluorescent Reporters in Medaka.无需克隆靶向青鳉鱼内源性基因座以生成荧光报告基因
Bio Protoc. 2025 Jun 20;15(12):e5360. doi: 10.21769/BioProtoc.5360.
3
CRISPR-Mediated Viral Gene Knock-In for Studying Viral-Host Interactions.用于研究病毒-宿主相互作用的CRISPR介导的病毒基因敲入

本文引用的文献

1
CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes.用于真核基因组操作的基于CRISPR的技术
Cell. 2017 Apr 20;169(3):559. doi: 10.1016/j.cell.2017.04.005.
2
The control of DNA repair by the cell cycle.细胞周期对 DNA 修复的调控。
Nat Cell Biol. 2016 Dec 23;19(1):1-9. doi: 10.1038/ncb3452.
3
Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.通过增强微同源末端连接实现基因盒在哺乳动物细胞和受精卵中的敲入。
Methods Mol Biol. 2025;2940:109-119. doi: 10.1007/978-1-0716-4615-1_10.
4
CRISPR/Cas system-mediated base editing in crops: recent developments and future prospects.CRISPR/Cas 系统介导的作物碱基编辑:最新进展与未来展望。
Plant Cell Rep. 2024 Oct 25;43(11):271. doi: 10.1007/s00299-024-03346-0.
5
Topoisomerase Inhibitors and PIM1 Kinase Inhibitors Improve Gene Editing Efficiency Mediated by CRISPR-Cas9 and Homology-Directed Repair.拓扑异构酶抑制剂和 PIM1 激酶抑制剂可提高 CRISPR-Cas9 介导的同源定向修复的基因编辑效率。
Molecules. 2024 Jun 18;29(12):2890. doi: 10.3390/molecules29122890.
6
CRISPR, CAR-T, and NK: Current applications and future perspectives.CRISPR、嵌合抗原受体T细胞(CAR-T)和自然杀伤细胞(NK):当前应用与未来展望。
Genes Dis. 2023 Sep 19;11(4):101121. doi: 10.1016/j.gendis.2023.101121. eCollection 2024 Jul.
7
Genetic Engineering and Genome Editing Advances to Enhance Floral Attributes in Ornamental Plants: An Update.用于增强观赏植物花卉特性的基因工程和基因组编辑进展:最新情况
Plants (Basel). 2023 Nov 27;12(23):3983. doi: 10.3390/plants12233983.
8
Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells.人类表皮干细胞中显性单纯性大疱性表皮松解症的等位基因特异性CRISPR-Cas9编辑
Mol Ther. 2024 Feb 7;32(2):372-383. doi: 10.1016/j.ymthe.2023.11.027. Epub 2023 Dec 5.
9
Genetic manipulation of betta fish.斗鱼的基因操作。
Front Genome Ed. 2023 Jul 21;5:1167093. doi: 10.3389/fgeed.2023.1167093. eCollection 2023.
10
Fast, precise and cloning-free knock-in of reporter sequences in vivo with high efficiency.高效、精确且无需克隆的体内报告序列基因敲入。
Development. 2023 Jun 15;150(12). doi: 10.1242/dev.201323. Epub 2023 Jun 29.
BMC Genomics. 2016 Nov 28;17(1):979. doi: 10.1186/s12864-016-3331-9.
4
In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration.通过CRISPR/Cas9介导的同源性非依赖靶向整合进行体内基因组编辑。
Nature. 2016 Dec 1;540(7631):144-149. doi: 10.1038/nature20565. Epub 2016 Nov 16.
5
Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA.通过改进gRNA、Cas9核酸酶和供体DNA的设计与递送,增强CRISPR/Cas9介导的精确基因组编辑。
J Biotechnol. 2017 Jan 10;241:136-146. doi: 10.1016/j.jbiotec.2016.11.011. Epub 2016 Nov 11.
6
Two Distinct Pathways Support Gene Correction by Single-Stranded Donors at DNA Nicks.两条不同途径支持单链供体在DNA切口处进行基因校正。
Cell Rep. 2016 Nov 8;17(7):1872-1881. doi: 10.1016/j.celrep.2016.10.049.
7
CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells.CRISPR/Cas9对人类造血干细胞β-珠蛋白基因的靶向作用。
Nature. 2016 Nov 17;539(7629):384-389. doi: 10.1038/nature20134. Epub 2016 Nov 7.
8
Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition.多重基因组编辑以产生对PD1抑制具有抗性的通用嵌合抗原受体T细胞
Clin Cancer Res. 2017 May 1;23(9):2255-2266. doi: 10.1158/1078-0432.CCR-16-1300. Epub 2016 Nov 4.
9
Chemical Inhibitors of Non-Homologous End Joining Increase Targeted Construct Integration in Cryptococcus neoformans.非同源末端连接的化学抑制剂增加新型隐球菌中靶向构建体的整合。
PLoS One. 2016 Sep 19;11(9):e0163049. doi: 10.1371/journal.pone.0163049. eCollection 2016.
10
Applications of CRISPR technologies in research and beyond.CRISPR技术在研究及其他领域的应用。
Nat Biotechnol. 2016;34(9):933-941. doi: 10.1038/nbt.3659. Epub 2016 Sep 8.