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SETMAR functions in illegitimate DNA recombination and non-homologous end joining

In anthropoid primates, SETMAR is a fusion between a methyltransferase gene and a domesticated DNA transposase. SETMAR has been found to be involved in several cellular functions including regulation of gene expression, DNA integration and DNA repair. These functions are thought to be mediated through the histone methyltransferase, the DNA binding and the nuclease activities of SETMAR. To better understand the cellular roles of SETMAR, we generated several U2OS cell lines expressing either wild type SETMAR or a truncated or mutated variant. We tested these cell lines with in vivo plasmid-based assays to determine the relevance of the different domains and activities of SETMAR in DNA integration and repair. We found that expressing the SET and MAR domains, but not wild type SETMAR, partially affect DNA integration and repair. The methyltransferase activity of SETMAR is also needed for an efficient DNA repair whereas we did not observe any requirement for the putative nuclease activity of SETMAR. Overall, our data support a non-essential function for SETMAR in DNA integration and repair.