非同源末端连接中DNA连接酶Ⅳ抑制剂研究进展  

Research progress of DNA ligase Ⅳ inhibitor in non-homologous end joining

作　　者：贺越 王秀梅 HE Yue;WANG Xiumei(The Affiliated People’s Hospital of Inner Mongolia Medical University,Hohhot 010020,China)

机构地区：[1]内蒙古医科大学附属人民医院内蒙古自治区肿瘤医院,内蒙古呼和浩特010020

出　　处：《陕西医学杂志》2023年第3期358-360,F0003,共4页Shaanxi Medical Journal

基　　金：内蒙古自治区草原英才项目(DC2100001472)。

摘　　要：DNA连接酶Ⅳ(LIG4)主要通过非同源末端连接(NHEJ)参与V(D)J重组和DNA双键断裂(DSB)修复,具有独特调控作用和广泛应用前景。研究发现,LIG4抑制剂在NHEJ中可作为增敏剂,与放化疗联合治疗肿瘤时具有较好的抗癌效果。此外,LIG4抑制剂还可作为一种有效的生化抑制剂介导CRISPR/Cas9基因编辑,有提高基因编辑效率的作用。近年来,许多研究基于此机制不断进行大规模药物筛选以发现新型抗癌药物,来为肿瘤治疗提供一种新思路。现对目前已报道的LIG4抑制剂及其衍生物的各种形式进行综述,并重点介绍目前应用较广的SCR7。DNA ligaseⅣ(LIG4)mainly participates in V(D)J recombination and DNA double-strand breaks(DSB)repair through non-homologous end joining(NHEJ),which has unique regulatory role and wide application prospect.It was found that LIG4 inhibitor can be used as sensitizer and has good anticancer effect when combined with radiotherapy and chemotherapy in the treatment of tumors.In addition,LIG4 inhibitor has also been reported as a potent biochemical inhibitor to improve gene editing efficiency in CRISPR/Cas9 gene editing.Recently,many studies have provided a new idea for the treatment of tumors through large-scale screening of drugs and the development of new anticancer drugs based on the NHEJ mechanism.In this review,we discuss the various forms of LIG4 inhibitors and their derivatives that have been reported so far,especially the widely used SCR7.

关 键 词：DNA连接酶Ⅳ抑制剂 非同源末端连接 DNA双键断裂 DNA修复 同源重组 肿瘤治疗 

分 类 号：R965.1[医药卫生—药理学]