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.