小分子化合物靶向DNA连接酶IV提高CRISPR/Cas9基因编辑效率的研究进展

doi:10.14088/j.cnki.issn0439-8114.2020.22.003

湖北农业科学 ›› 2020, Vol. 59 ›› Issue (22): 13-19.doi: 10.14088/j.cnki.issn0439-8114.2020.22.003

小分子化合物靶向DNA连接酶IV提高CRISPR/Cas9基因编辑效率的研究进展

肖红卫, 毕延震

动物胚胎工程与分子育种湖北重点实验室/湖北省农业科学院畜牧兽医研究所,武汉 430064

收稿日期:2020-04-24 出版日期:2020-11-25 发布日期:2020-12-30
通讯作者: 毕延震,主要从事动物生物技术研究,(电子信箱)sukerbyz@126.com
作者简介:肖红卫(1979-),男,江苏盐城人,副研究员,硕士,主要从事动物生物技术研究,(电话)15927164615(电子信箱)xiaohongwei2003@163.com
基金资助:
转基因生物新品种培育重大专项(2016ZX08010003-006);湖北省自然科学基金杰出青年项目(2018CFA043);湖北省技术创新重大专项(2019ABA084);湖北省创新中心项目(2020-620-000-001-20);中国科学院战略性科技先导专项(XDA24030204);湖北省农业科学院领军人才培养计划项目(L2018015)

Progress of small molecule compounds targeting DNA ligase IV to improve the efficiency of CRISPR/Cas9 genome editing

XIAO Hong-wei, BI Yan-zhen

Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding,Institute of Animal Husbandry and Veterinary Research,Hubei Academy of Agricultural Sciences,Wuhan 430064,China

Received:2020-04-24 Online:2020-11-25 Published:2020-12-30

摘要/Abstract

摘要： 基因编辑工具能够在DNA链上制造特定位点双链断裂(Double-strand breaks,DSB)。细胞内具有修复DSB的2种不同途径,即同源重组(HDR)和非同源末端连接(NHEJ)。NHEJ与HDR之间相互竞争,互为替代DNA修复途径。DNA连接酶IV参与NHEJ途径并发挥重要作用。DNA连接酶IV抑制剂可以抑制DNA修复通路中NHEJ的效率,同时可以提高HDR的效率。为了优选小分子化合物实现更有效的基因定点插入,综述了SCR7、NU7026、白藜芦醇、L755507这4种不同的小分子化合物在CRISPR/Cas9基因编辑效率上的研究,归纳了这4种小分子化合物在其中发挥的作用,并用生物信息学软件模拟所用小分子化合物与DNA连接酶IV的对接。在此基础上,对这4种小分子化合物提高基因编辑效率的研究前景进行了展望。

关键词: 双链断裂, 同源重组, 非同源末端连接, DNA连接酶IV, 小分子化合物

Abstract: Gene-editing-tools can create double-strand breaks (DSB) at specific sites on the DNA chains.There are two different ways to repair DSB in cells,namely homologous recombination (HDR) and non-homologous end joining (NHEJ).NHEJ pathway and HDR pathway compete with each other as alternative DNA repair pathways.DNA ligase IV acts an important role in the NHEJ pathway.Inhibitors of DNA ligase IV can inhibiting the NHEJ efficiency while improving HDR efficiency in the DNA repair pathway.To optimize small-molecule compounds for more effective site-specific insertion of genes,the studies on the four different chemicals SCR7,NU7026,resveratrol and L755507 were reviewed,and these four small-molecule compounds in gene-editing were summarized.Among them,the bioinformatics software was used to simulate the docking of these four chemicals with DNA ligase IV.Based on these,the small molecule compounds used to improving gene editing efficiency was prospected.

Key words: DSB(double strand break), HDR(Homologous directed recombination), NHEJ (Nonhomologous end joining), DNA ligase IV, small molecule compound

中图分类号:

肖红卫, 毕延震. 小分子化合物靶向DNA连接酶IV提高CRISPR/Cas9基因编辑效率的研究进展[J]. 湖北农业科学, 2020, 59(22): 13-19.

XIAO Hong-wei, BI Yan-zhen. Progress of small molecule compounds targeting DNA ligase IV to improve the efficiency of CRISPR/Cas9 genome editing[J]. HUBEI AGRICULTURAL SCIENCES, 2020, 59(22): 13-19.

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小分子化合物靶向DNA连接酶IV提高CRISPR/Cas9基因编辑效率的研究进展

Progress of small molecule compounds targeting DNA ligase IV to improve the efficiency of CRISPR/Cas9 genome editing

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