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

The nucleo-mitochondrial dual-localized proteins can act as gene expression regulators; however, few instances of these proteins have been described in plants. Arabidopsis (Arabidopsis thaliana) 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. PHB3 is up-regulated by DNA damage agents, and the stress-induced PHB3 proteins accumulate in the nucleus. Loss of function of PHB3 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 phb3 mutant shows aberrant cell division and altered expression of cell cycle-related genes, such as CycB1 and Cyclin dependent kinase 1 Moreover, the minichromosome maintenance (MCM) genes, e.g. MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7, are up-regulated in the phb3 mutant. Reducing the MCM2 expression level substantially recovers the DNA damage in the phb3 mutant and partially rescues the altered cell proliferation and root deficiency of phb3 seedlings. PHB3 acts as a transcriptional coregulator that represses MCM2 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 MCM2 expression to sustain genome integrity and cell proliferation for stem cell niche maintenance in Arabidopsis.