Function and molecular mechanisms of APE2 in genome and epigenome integrity.

Function and molecular mechanisms of APE2 in genome and epigenome integrity.
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DOI:
10.1016/j.mrrev.2020.108347
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发表时间:
2021-01
期刊:
Mutation research. Reviews in mutation research
影响因子:
--
通讯作者:
Yan S
Yan S
中科院分区:
其他
文献类型:
--
作者:
Lin Y;McMahon A;Driscoll G;Bullock S;Zhao J;Yan S

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APE2 在维持基因组和表观基因组完整性方面发挥着重要作用。在过去的几年中,一系列研究表明了APE2的关键作用和功能。我们力求对 APE2 基因组和表观基因组完整性的多个方面进行首次全面综述。我们首先总结了 APE2 中不同的功能域或基序,包括 EEP(核酸内切酶/核酸外切酶/磷酸酶)结构域、PIP 盒和 Zf-GRF 基序,这些基序来自 8 个物种(即智人、小家鼠、非洲爪蟾、海鞘、拟南芥、粟酒裂殖酵母、酿酒酵母和克氏锥虫)。然后我们分析各种 APE2 核酸酶活性和相关 DNA 底物,包括 AP 核酸内切酶、3'-磷酸二酯酶、3'-磷酸酶和 3'-5' 核酸外切酶活性。我们还检查了几种 APE2 相互作用蛋白,包括 PCNA、Chk1、APE1、Myh1 和同源重组 (HR) 因子,如 Rad51、Rad52、BRCA1、BRCA2 和 BARD1。此外,我们还深入了解了 APE2 在各种 DNA 修复途径(碱基切除修复、单链断裂修复和双链断裂修复)、DNA 损伤反应 (DDR) 途径(ATR-Chk1 和 p53 依赖性)、免疫球蛋白类开关重组和体细胞超突变以及主动 DNA 去甲基化中的作用。最后,我们总结了 APE2 在生长、发育和疾病中的关键功能。在这篇综述中,我们提供了第一个全面的视角,剖析了多功能蛋白 APE2 在基因组和表观基因组完整性方面的各个方面。
APE2 is a rising vital player in the maintenance of genome and epigenome integrity. In the past several years, a series of studies have shown the critical roles and functions of APE2. We seek to provide the first comprehensive review on several aspects of APE2 in genome and epigenome integrity. We first summarize the distinct functional domains or motifs within APE2 including EEP (endonuclease/exonuclease/phosphatase) domain, PIP box and Zf-GRF motifs from eight species (i.e., Homo sapiens, Mus musculus, Xenopus laevis, Ciona intestinalis, Arabidopsis thaliana, Schizosaccharomyces pombe, Saccharomyces cerevisiae, and Trypanosoma cruzi). Then we analyze various APE2 nuclease activities and associated DNA substrates, including AP endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-5' exonuclease activities. We also examine several APE2 interaction proteins, including PCNA, Chk1, APE1, Myh1, and homologous recombination (HR) factors such as Rad51, Rad52, BRCA1, BRCA2, and BARD1. Furthermore, we provide insights into the roles of APE2 in various DNA repair pathways (base excision repair, single-strand break repair, and double-strand break repair), DNA damage response (DDR) pathways (ATR-Chk1 and p53-dependent), immunoglobulin class switch recombination and somatic hypermutation, as well as active DNA demethylation. Lastly, we summarize critical functions of APE2 in growth, development, and diseases. In this review, we provide the first comprehensive perspective which dissects all aspects of the multiple-function protein APE2 in genome and epigenome integrity.
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