The nuclease FAN1 is involved in DNA crosslink repair in Arabidopsis thaliana independently of the nuclease MUS81.
Bottom Line: No FAN1 homolog is present in Drosophila and Saccharomyces cerevisiae.Both the virus-type replication-repair nuclease and the ubiquitin-binding ubiquitin-binding zinc finger domains are essential for this function.Mutations in both FAN1 and the endonuclease MUS81 resulted in greater sensitivity against CLs than in the respective single mutants.
Affiliation: Botanical Institute II, Karlsruhe Institute of Technology, Hertzstrasse 16, Karlsruhe, 76187, Germany.Show MeSH
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Mentions: A search for homologs of the human FAN1 gene in A. thaliana using BLAST analyses revealed a single hit at the locus AT1G48360. AtFAN1 has a length of 4382 bp between the start and stop codon; the gene is composed of 15 exons and 14 introns (Figure 1A). The predicted protein (Q5XVJ4) has a length of 891 aa and contains a HIRAN domain near its C-terminus (PFAM08797) and a VRR nuclease domain at its N-terminus (PFAM08774) (Figure 1B). The human homolog contains a SAP domain in a similar position as the HIRAN domain. Both of these domains are postulated to be involved in DNA binding. Using domain search algorithms, a UBZ domain could not be detected in AtFAN1; however, protein sequence alignments containing HsFAN1 and AtFAN1 revealed several conserved and similar amino acids in the region containing the human UBZ domain. Therefore, we assume that AtFAN1 might contain a functional UBZ domain (Figure 1C). To determine the evolutionary relationship between different FAN1 homologs, a phylogenetic tree was derived from a ClustalOmega (http://www.ebi.ac.uk/Tools/msa/clustalo/) multiple sequence alignment containing sequences of different FAN1 proteins from animals, plants and fungi. This phylogenetic tree was calculated using the maximum likelihood method in MEGA 6.0 (44) (Figure 2). In general, FAN1 can be found in all plant species tested. Therefore, this protein is likely of some biological importance for plants in general. Within the plant clade, the FAN1 homologs follow the evolutionary relationship of the species analyzed. For example, FAN1 from A. thaliana and tomato (Solanum lycopersicum) are closely related. These two sequences form a clade with the basal angiosperm Amborella trichpoda. FAN1 homologs in rice (Oryza sativa) and the moss Physcomitrella patens are more distantly related to Arabidopsis FAN1. The phylogenetic relationship is also conserved within animals and fungi. Surprisingly, the relationship between animal and plant FAN1 homologs seems to be closer than the relationship between the animal and fungal FAN1 homologs.
Affiliation: Botanical Institute II, Karlsruhe Institute of Technology, Hertzstrasse 16, Karlsruhe, 76187, Germany.