近日，上海生科院植生生态所黄海课题组科研人员与英国剑桥大学及John Innes Centre的Janneke Balk博士研究组合作在国际植物科学领域权威期刊《The Plant Cell》发表了题为“The DUF59 family gene AE7 acts in the cytosolic iron-sulfur cluster assembly pathway to maintain nuclear genome integrity in Arabidopsis”的研究论文，揭示了植物细胞质铁-硫(Fe-S)簇组装(CIA)途径对于核基因组完整性的维持具有重要作用。
在真核细胞中，维持基因组完整性是有丝分裂细胞周期正常运转和生物体正常生长发育的前提。目前对细胞核内维持基因组完整性机制的研究已较为清楚，然而对于细胞核外因素在维持基因组完整性中的作用仍了解较少。
植生生态所黄海课题组科研人员先前的研究发现，在拟南芥中一个功能未知但进化上高度保守的DUF59基因家族成员AE7是细胞周期正常运转和叶极性建成所必需的(Yuan et al., 2010, Plant Journal)。在本项研究中，他们发现拟南芥AE7基因的突变可导致基因组完整性遭到破坏，细胞内DNA损伤增多、体细胞内同源重组频率增加，从而激活DNA损伤修复反应导致细胞周期停滞。AE7可与CIA1, NAR1和MET18等蛋白形成复合体，组成植物CIA途径中的一个核心组分，参与细胞质和细胞核内含Fe-S簇蛋白的组装形成，而许多DNA复制和修复相关的核蛋白需要Fe-S簇辅基才能发挥正常功能。因此，CIA核心组分的缺失将严重影响细胞周期正常运转。植物CIA途径的功能依赖于线粒体中Fe-S簇组装机器和定位于线粒体膜上的转运蛋白ATM3。他们的研究还发现拟南芥ATM3也是维持核基因组完整性所必需的，因而这项工作还将植物线粒体的功能与维持核基因组完整性的机制联系起来。
此项研究得到了国家自然科学基金委、中国科学院和国家科技部等项目的支持。(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.
