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: We show that, in Arabidopsis, at least two of the nucleases tested in this study are not epistatic. These nucleases are involved in different CL repair pathways. MUS81 and FAN1 differ in their incision specificities; however, these two enzymes are able to process similar DNA structures, such as nicked Holliday junctions, although to different products. It has been speculated that one nuclease could be responsible for an incision on the 5′ DNA strand of the interstrand CL lesion and a second nuclease incises the 3′ strand of the CL. Therefore, FAN1 and MUS81 could work in a common pathway. In Arabidopsis, this seems not to be the case. In contrast, FAN1 might act as one of the incision nucleases in the first step of the canonical CL pathway. In this scenario, MUS81 is responsible for the processing of more complex DNA structures or intermediates that cannot be processed by other nucleases involved in the CL pathways. Our previous studies of MUS81 indicate that this nuclease is involved in the removal of replicative DNA intermediates that would otherwise block replication. This is also documented by the fact that the double mutants of MUS81 and either RECQ4A or FANCM result in synthetic lethality phenotypes (24,32,59). If certain types of DNA damage cannot be removed by the action of specific sophisticated DNA helicases, the MUS81 nuclease might act as a safeguard and a universal tool to remove all intermediates that would otherwise result in dead ends. A model of how Arabidopsis FAN1 might work in interstrand CL repair in relation to all other factors tested in this study is shown in Figure 7.
Affiliation: Botanical Institute II, Karlsruhe Institute of Technology, Hertzstrasse 16, Karlsruhe, 76187, Germany.