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SCR7,一种有效的癌症治疗剂,也是一种非同源 DNA 末端连接的生化抑制剂。

SCR7, a potent cancer therapeutic agent and a biochemical inhibitor of nonhomologous DNA end-joining.

机构信息

Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.

Manipal Academy of Higher Education, Manipal, India.

出版信息

Cancer Rep (Hoboken). 2021 Jun;4(3):e1341. doi: 10.1002/cnr2.1341. Epub 2021 Jan 26.

DOI:10.1002/cnr2.1341
PMID:33496064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8222562/
Abstract

BACKGROUND

DNA double-strand breaks (DSBs) are harmful to the cell as it could lead to genomic instability and cell death when left unrepaired. Homologous recombination and nonhomologous end-joining (NHEJ) are two major DSB repair pathways, responsible for ensuring genome integrity in mammals. There have been multiple efforts using small molecule inhibitors to target these DNA repair pathways in cancers. SCR7 is a very well-studied anticancer molecule that blocks NHEJ by targeting one of the critical enzymes, Ligase IV.

RECENT FINDINGS

In this review, we have highlighted the anticancer effects of SCR7 as a single agent and in combination with other chemotherapeutic agents and radiation. SCR7 blocked NHEJ effectively both in vitro and ex vivo. SCR7 has been used for biochemical studies like chromosomal territory resetting and in understanding the role of repair proteins in cell cycle phases. Various forms of SCR7 and its derivatives are discussed. SCR7 is also used as a potent biochemical inhibitor of NHEJ, which has found its application in improving genome editing using a CRISPR-Cas system.

CONCLUSION

SCR7 is a potent NHEJ inhibitor with unique properties and wide applications as an anticancer agent. Most importantly, SCR7 has become a handy aid for improving genome editing across different model systems.

摘要

背景

DNA 双链断裂(DSBs)对细胞是有害的,因为如果不修复,可能会导致基因组不稳定和细胞死亡。同源重组和非同源末端连接(NHEJ)是两种主要的 DSB 修复途径,负责确保哺乳动物基因组的完整性。已经有许多使用小分子抑制剂靶向这些 DNA 修复途径的癌症研究。SCR7 是一种研究得非常透彻的抗癌分子,通过靶向关键酶之一 Ligase IV 来阻断 NHEJ。

最近的发现

在这篇综述中,我们强调了 SCR7 作为单一药物以及与其他化疗药物和放射治疗联合使用的抗癌作用。SCR7 在体外和体内都能有效地阻断 NHEJ。SCR7 已被用于生化研究,如染色体领域重置,并用于了解修复蛋白在细胞周期各阶段的作用。讨论了各种形式的 SCR7 及其衍生物。SCR7 也是 NHEJ 的有效生化抑制剂,已被用于改进使用 CRISPR-Cas 系统的基因组编辑。

结论

SCR7 是一种有效的 NHEJ 抑制剂,具有独特的性质和广泛的应用作为抗癌剂。最重要的是,SCR7 已成为不同模型系统中改进基因组编辑的得力助手。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/cd4087116c3f/CNR2-4-e1341-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/2acfa145a46c/CNR2-4-e1341-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/a285afabecf7/CNR2-4-e1341-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/96340aba0292/CNR2-4-e1341-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/cd4087116c3f/CNR2-4-e1341-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/2acfa145a46c/CNR2-4-e1341-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/a285afabecf7/CNR2-4-e1341-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/96340aba0292/CNR2-4-e1341-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/8222562/cd4087116c3f/CNR2-4-e1341-g002.jpg

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本文引用的文献

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Oncogene. 2020 Oct;39(41):6393-6405. doi: 10.1038/s41388-020-01445-2. Epub 2020 Sep 3.
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Inhibitors of DNA double-strand break repair at the crossroads of cancer therapy and genome editing.处于癌症治疗与基因组编辑交叉点的DNA双链断裂修复抑制剂。
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NHEJ inhibitor SCR7 and its different forms: Promising CRISPR tools for genome engineering.
双链DNA断裂修复:分子机制与治疗靶点
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Mutational Signatures in Gastric Cancer and Their Clinical Implications.胃癌中的突变特征及其临床意义。
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Strategies for High-Efficiency Mutation Using the CRISPR/Cas System.使用CRISPR/Cas系统进行高效突变的策略。
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NHEJ 抑制剂 SCR7 及其不同形式:用于基因组工程的有前途的 CRISPR 工具。
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Identification and characterization of novel SCR7-based small-molecule inhibitor of DNA end-joining, SCR130 and its relevance in cancer therapeutics.鉴定和表征基于 SCR7 的新型 DNA 末端连接小分子抑制剂 SCR130 及其在癌症治疗中的相关性。
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