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劍橋大學(xué)及John Innes Centre的Janneke Balk博士研究組合作在國際植物科學(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,,揭示了植物細胞質(zhì)鐵-硫(Fe-S)簇組裝(CIA)途徑對于核基因組完整性的維持具有重要作用。
在真核細胞中,,維持基因組完整性是有絲分裂細胞周期正常運轉(zhuǎn)和生物體正常生長發(fā)育的前提,。目前對細胞核內(nèi)維持基因組完整性機制的研究已較為清楚,然而對于細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),,在擬南芥中一個功能未知但進化上高度保守的DUF59基因家族成員AE7是細胞周期正常運轉(zhuǎn)和葉極性建成所必需的(Yuan et al., 2010, Plant Journal)。在本項研究中,,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,,細胞內(nèi)DNA損傷增多、體細胞內(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途徑中的一個核心組分,,參與細胞質(zhì)和細胞核內(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)重影響細胞周期正常運轉(zhuǎn),。植物CIA途徑的功能依賴于線粒體中Fe-S簇組裝機器和定位于線粒體膜上的轉(zhuǎn)運蛋白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,,因而這項工作還將植物線粒體的功能與維持核基因組完整性的機制聯(lián)系起來,。
此項研究得到了國家自然科學(xué)基金委、中國科學(xué)院和國家科技部等項目的支持,。(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.