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秀丽隐杆线虫 NSE3 同源物(MAGE-1)参与基因组稳定性,并在减数分裂过程中发挥姐妹染色单体间重组的作用。

Caenorhabditis elegans NSE3 homolog (MAGE-1) is involved in genome stability and acts in inter-sister recombination during meiosis.

机构信息

State Key Laboratory of Non-food Biomass and Enzyme Technology, Guangxi Academy of Sciences, Nanning 530007, China.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Genetics. 2023 Oct 4;225(2). doi: 10.1093/genetics/iyad149.

Abstract

Melanoma antigen (MAGE) genes encode for a family of proteins that share a common MAGE homology domain. These genes are conserved in eukaryotes and have been linked to a variety of cellular and developmental processes including ubiquitination and oncogenesis in cancer. Current knowledge on the MAGE family of proteins mainly comes from the analysis of yeast and human cell lines, and their functions have not been reported at an organismal level in animals. Caenorhabditis elegans only encodes 1 known MAGE gene member, mage-1 (NSE3 in yeast), forming part of the SMC-5/6 complex. Here, we characterize the role of mage-1/nse-3 in mitosis and meiosis in C. elegans. mage-1/nse-3 has a role in inter-sister recombination repair during meiotic recombination and for preserving chromosomal integrity upon treatment with a variety of DNA-damaging agents. MAGE-1 directly interacts with NSE-1 and NSE-4. In contrast to smc-5, smc-6, and nse-4 mutants which cause the loss of NSE-1 nuclear localization and strong cytoplasmic accumulation, mage-1/nse-3 mutants have a reduced level of NSE-1::GFP, remnant NSE-1::GFP being partially nuclear but largely cytoplasmic. Our data suggest that MAGE-1 is essential for NSE-1 stability and the proper functioning of the SMC-5/6 complex.

摘要

黑色素瘤相关抗原(MAGE)基因编码一类具有共同 MAGE 同源结构域的蛋白质。这些基因在真核生物中是保守的,与多种细胞和发育过程有关,包括泛素化和癌症中的肿瘤发生。目前对 MAGE 蛋白家族的了解主要来自于酵母和人类细胞系的分析,它们的功能在动物的个体水平上尚未得到报道。秀丽隐杆线虫只编码 1 个已知的 MAGE 基因成员,mage-1(酵母中的 NSE3),形成 SMC-5/6 复合物的一部分。在这里,我们描述了 mage-1/nse-3 在秀丽隐杆线虫有丝分裂和减数分裂中的作用。mage-1/nse-3 在减数分裂重组过程中的姐妹染色单体间重组修复中发挥作用,并在受到各种 DNA 损伤剂处理时保持染色体完整性。MAGE-1 与 NSE-1 和 NSE-4 直接相互作用。与导致 NSE-1 核定位丧失和强烈细胞质积累的 smc-5、smc-6 和 nse-4 突变体不同,mage-1/nse-3 突变体中 NSE-1::GFP 的水平降低,残留的 NSE-1::GFP 部分核定位,但大部分在细胞质中。我们的数据表明,MAGE-1 对 NSE-1 的稳定性和 SMC-5/6 复合物的正常功能至关重要。

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本文引用的文献

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The Smc5/6 complex is a DNA loop-extruding motor.Smc5/6 复合物是一种 DNA 环挤出分子马达。
Nature. 2023 Apr;616(7958):843-848. doi: 10.1038/s41586-023-05963-3. Epub 2023 Apr 19.
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Emerging roles of the MAGE protein family in stress response pathways.MAGE 蛋白家族在应激反应途径中的新作用。
J Biol Chem. 2020 Nov 20;295(47):16121-16155. doi: 10.1074/jbc.REV120.008029. Epub 2020 Sep 13.

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