近日,，上海生科院植生生態(tài)所黃海課題組科研人員與英國(guó)劍橋大學(xué)及John Innes Centre的Janneke Balk博士研究組合作在國(guó)際植物科學(xué)領(lǐng)域權(quán)威期刊《The Plant Cell》發(fā)表了題為“The DUF59 family gene AE7 acts in the cytosolic iron-sulfur cluster assembly pathway to maintain nuclear genome integrity in Arabidopsis”的研究論文,，揭示了植物細(xì)胞質(zhì)鐵-硫(Fe-S)簇組裝(CIA)途徑對(duì)于核基因組完整性的維持具有重要作用。
在真核細(xì)胞中,，維持基因組完整性是有絲分裂細(xì)胞周期正常運(yùn)轉(zhuǎn)和生物體正常生長(zhǎng)發(fā)育的前提,。目前對(duì)細(xì)胞核內(nèi)維持基因組完整性機(jī)制的研究已較為清楚，然而對(duì)于細(xì)胞核外因素在維持基因組完整性中的作用仍了解較少,。
植生生態(tài)所黃海課題組科研人員先前的研究發(fā)現(xiàn),，在擬南芥中一個(gè)功能未知但進(jìn)化上高度保守的DUF59基因家族成員AE7是細(xì)胞周期正常運(yùn)轉(zhuǎn)和葉極性建成所必需的(Yuan et al., 2010, Plant Journal)。在本項(xiàng)研究中,，他們發(fā)現(xiàn)擬南芥AE7基因的突變可導(dǎo)致基因組完整性遭到破壞,，細(xì)胞內(nèi)DNA損傷增多、體細(xì)胞內(nèi)同源重組頻率增加,，從而激活DNA損傷修復(fù)反應(yīng)導(dǎo)致細(xì)胞周期停滯,。AE7可與CIA1, NAR1和MET18等蛋白形成復(fù)合體，組成植物CIA途徑中的一個(gè)核心組分,，參與細(xì)胞質(zhì)和細(xì)胞核內(nèi)含F(xiàn)e-S簇蛋白的組裝形成,，而許多DNA復(fù)制和修復(fù)相關(guān)的核蛋白需要Fe-S簇輔基才能發(fā)揮正常功能。因此,，CIA核心組分的缺失將嚴(yán)重影響細(xì)胞周期正常運(yùn)轉(zhuǎn),。植物CIA途徑的功能依賴(lài)于線(xiàn)粒體中Fe-S簇組裝機(jī)器和定位于線(xiàn)粒體膜上的轉(zhuǎn)運(yùn)蛋白ATM3。他們的研究還發(fā)現(xiàn)擬南芥ATM3也是維持核基因組完整性所必需的,，因而這項(xiàng)工作還將植物線(xiàn)粒體的功能與維持核基因組完整性的機(jī)制聯(lián)系起來(lái),。
此項(xiàng)研究得到了國(guó)家自然科學(xué)基金委、中國(guó)科學(xué)院和國(guó)家科技部等項(xiàng)目的支持,。(生物谷Bioon.com)
DOI:10.1105/tpc.112.102608
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PMID:
The DUF59 Family Gene AE7 Acts in the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Maintain Nuclear Genome Integrity in Arabidopsis
Dexian Luoa, Delphine G. Bernardb, Janneke Balkb,c,d,1, Huang Haia and Xiaofeng Cuia,1,2
Eukaryotic organisms have evolved a set of strategies to safeguard genome integrity, but the underlying mechanisms remain poorly understood. Here, we report that ASYMMETRIC LEAVES1/2 ENHANCER7 (AE7), an Arabidopsis thaliana gene encoding a protein in the evolutionarily conserved Domain of Unknown Function 59 family, participates in the cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway to maintain genome integrity. The severe ae7-2 allele is embryo lethal, whereas plants with the weak ae7 (ae7-1) allele are viable but exhibit highly accumulated DNA damage that activates the DNA damage response to arrest the cell cycle. AE7 is part of a protein complex with CIA1, NAR1, and MET18, which are highly conserved in eukaryotes and are involved in the biogenesis of cytosolic and nuclear Fe-S proteins. ae7-1 plants have lower activities of the cytosolic [4Fe-4S] enzyme aconitase and the nuclear [4Fe-4S] enzyme DNA glycosylase ROS1. Additionally, mutations in the gene encoding the mitochondrial ATP binding cassette transporter ATM3/ABCB25, which is required for the activity of cytosolic Fe-S enzymes in Arabidopsis, also result in defective genome integrity similar to that of ae7-1. These results indicate that AE7 is a central member of the CIA pathway, linking plant mitochondria to nuclear genome integrity through assembly of Fe-S proteins.
