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核抑制素 3 通过微染色体维持蛋白 2 维持根分生组织的基因组完整性和细胞增殖。

Nuclear Prohibitin3 Maintains Genome Integrity and Cell Proliferation in the Root Meristem through Minichromosome Maintenance 2.

机构信息

Guangdong Key Laboratory of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631, China.

Guangdong Key Laboratory of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631, China

出版信息

Plant Physiol. 2019 Apr;179(4):1669-1691. doi: 10.1104/pp.18.01463. Epub 2019 Jan 23.

Abstract

The nucleo-mitochondrial dual-localized proteins can act as gene expression regulators; however, few instances of these proteins have been described in plants. Arabidopsis () PROHIBITIN 3 (PHB3) is involved in stress responses and developmental processes, but it is unknown how these roles are achieved at the molecular level in the nucleus. In this study, we show that nucleo-mitochondrial PHB3 plays an essential role in regulating genome stability and cell proliferation. is up-regulated by DNA damage agents, and the stress-induced PHB3 proteins accumulate in the nucleus. Loss of function of results in DNA damage and defective maintenance of the root stem cell niche. Subsequently, the expression patterns and levels of the root stem cell regulators are altered and down-regulated, respectively. In addition, the mutant shows aberrant cell division and altered expression of cell cycle-related genes, such as and Moreover, the minichromosome maintenance (MCM) genes, e.g. , , , , , and , are up-regulated in the mutant. Reducing the expression level substantially recovers the DNA damage in the mutant and partially rescues the altered cell proliferation and root deficiency of seedlings. PHB3 acts as a transcriptional coregulator that represses expression by competitively binding to the promoter E2F-cis-acting elements with E2Fa so as to modulate primary root growth. Collectively, these findings indicate that nuclear-localized PHB3 acts as a transcriptional coregulator that suppresses expression to sustain genome integrity and cell proliferation for stem cell niche maintenance in Arabidopsis.

摘要

核-线粒体双重定位蛋白可以作为基因表达调控因子;然而,在植物中很少有这些蛋白的描述。拟南芥(Arabidopsis)PROHIBITIN 3(PHB3)参与应激反应和发育过程,但在细胞核中,这些作用如何在分子水平上实现尚不清楚。在这项研究中,我们表明核-线粒体 PHB3 在调节基因组稳定性和细胞增殖方面起着至关重要的作用。在受到 DNA 损伤剂的刺激时,表达上调,并且应激诱导的 PHB3 蛋白在核内积累。的功能丧失导致 DNA 损伤和根干细胞龛的维持缺陷。随后,根干细胞调节因子的表达模式和水平分别发生改变和下调。此外,突变体表现出异常的细胞分裂和细胞周期相关基因(如和)的表达改变。此外,微染色体维持(MCM)基因,例如,在突变体中上调。在突变体中,表达水平显著降低可大大恢复 DNA 损伤,并部分挽救突变体中改变的细胞增殖和根缺失。PHB3 作为转录共激活因子,通过与 E2Fa 竞争结合 E2F-cis 作用元件来抑制表达,从而调节主根生长。总之,这些发现表明,核定位的 PHB3 作为转录共激活因子,通过抑制表达来维持基因组完整性和细胞增殖,以维持拟南芥干细胞龛的维持。

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