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DNA修复核酸内切酶:生理作用及作为药物靶点的潜力

DNA Repair Endonucleases: Physiological Roles and Potential as Drug Targets.

作者信息

Doherty Rachel, Madhusudan Srinivasan

机构信息

Laboratory of Molecular Oncology, Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, UK.

Laboratory of Molecular Oncology, Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, UK

出版信息

J Biomol Screen. 2015 Aug;20(7):829-41. doi: 10.1177/1087057115581581. Epub 2015 Apr 15.

Abstract

Genomic DNA is constantly exposed to endogenous and exogenous damaging agents. To overcome these damaging effects and maintain genomic stability, cells have robust coping mechanisms in place, including repair of the damaged DNA. There are a number of DNA repair pathways available to cells dependent on the type of damage induced. The removal of damaged DNA is essential to allow successful repair. Removal of DNA strands is achieved by nucleases. Exonucleases are those that progressively cut from DNA ends, and endonucleases make single incisions within strands of DNA. This review focuses on the group of endonucleases involved in DNA repair pathways, their mechanistic functions, roles in cancer development, and how targeting these enzymes is proving to be an exciting new strategy for personalized therapy in cancer.

摘要

基因组DNA不断受到内源性和外源性损伤因子的影响。为了克服这些损伤效应并维持基因组稳定性,细胞具备强大的应对机制,包括修复受损的DNA。根据所诱导损伤的类型,细胞有多种DNA修复途径可供选择。去除受损DNA对于成功修复至关重要。DNA链的去除是通过核酸酶实现的。外切核酸酶是那些从DNA末端逐步切割的酶,而内切核酸酶则在DNA链内进行单一切口。本综述聚焦于参与DNA修复途径的内切核酸酶群体、它们的机制功能、在癌症发展中的作用,以及靶向这些酶如何正成为一种令人兴奋的癌症个性化治疗新策略。

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