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Apurinic/Apyrimidinic Endonuclease 2 (APE2): An ancillary enzyme for contextual base excision repair mechanisms to preserve genome stability
Biochimie ( IF 3.3 ) Pub Date : 2021-07-21 , DOI: 10.1016/j.biochi.2021.07.006
Sima Chaudhari 1 , Akshay P Ware 2 , Pradyumna Jayaram 1 , Sankar Prasad Gorthi 3 , Sherif F El-Khamisy 4 , Kapaettu Satyamoorthy 1
Affiliation  

The genome of living organisms frequently undergoes various types of modifications which are recognized and repaired by the relevant repair mechanisms. These repair pathways are increasingly being deciphered to understand the mechanisms. Base excision repair (BER) is indispensable to maintain genome stability. One of the enigmatic repair proteins of BER, Apurinic/Apyrimidinic Endonuclease 2 (APE2), like APE1, is truly multifunctional and demonstrates the independent and non-redundant function in maintaining the genome integrity. APE2 is involved in ATR-Chk1 mediated DNA damage response. It also resolves topoisomerase1 mediated cleavage complex intermediate which is formed while repairing misincorporated ribonucleotides in the absence of functional RNase H2 mediated excision repair pathway. BER participates in the demethylation pathway and the role of Arabidopsis thaliana APE2 is demonstrated in this process. Moreover, APE2 is synthetically lethal to BRCA1, BRCA2, and RNase H2, and its homolog, APE1 fails to complement the function. Hence, the role of APE2 is not just an alternate to the repair mechanisms but has implications in diverse functional pathways related to the maintenance of genome integrity. This review analyses genomic features of APE2 and delineates its enzyme function as error-prone as well as efficient and accurate repair protein based on the studies on mammalian or its homolog proteins from model systems such as Arabidopsis thaliana, Schizosaccharomyces pombe, Trypanosoma curzi, Xenopus laevis, Danio rerio, Mus musculus, and Homo sapiens.



中文翻译:

无嘌呤/无嘧啶核酸内切酶 2 (APE2):一种辅助酶,用于上下文碱基切除修复机制,以保持基因组稳定性

生物体的基因组经常经历各种类型的修饰,这些修饰被相关的修复机制识别和修复。这些修复途径越来越多地被破译以了解其机制。碱基切除修复(BER)对于维持基因组稳定性是必不可少的。BER 的神秘修复蛋白之一,无嘌呤/无嘧啶核酸内切酶 2 (APE2) 与 APE1 一样,具有真正的多功能性,并在维持基因组完整性方面表现出独立和非冗余的功能。APE2 参与 ATR-Chk1 介导的 DNA 损伤反应。它还解决了拓扑异构酶 1 介导的切割复合物中间体,该中间体是在没有功能性 RNase H2 介导的切除修复途径的情况下修复错误掺入的核糖核苷酸时形成的。在这个过程中证明了拟南芥APE2。此外,APE2 对 BRCA1、BRCA2 和 RNase H2 具有综合致死性,其同源物 APE1 无法补充该功能。因此,APE2 的作用不仅是修复机制的替代物,而且在与维持基因组完整性相关的多种功能途径中也有影响。这篇综述基于对拟南芥、粟酒裂殖酵母、锥虫、非洲爪蟾等模型系统的哺乳动物或其同源蛋白的研究,分析了APE2的基因组特征,并将其酶功能描述为容易出错以及高效准确的修复蛋白。, Danio rerio , Mus musculusHomo sapiens。

更新日期:2021-07-24
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