SETMAR

SETMAR contains a SET domain that confers its histone methyltransferase activity, on Lys-4 and Lys-36 of Histone H3, both of which are specific tags for epigenetic activation. It has been identified as a repair protein as it mediates dimethylation at Lys-36 at double-strand break locations, a signal enhancing NHEJ repair.^[7][8]

Anthropoid primates, including humans, have a version of the protein fused to a Mariner/Tc1 transposase. This fusion region provides the DNA-binding abilities for the protein as well as some nuclease activity. The transposase activity is lost due to the presence of several inactivating mutations,^[9] including the D610N mutation.^[10][11] However, the domesticated transposase domain retains its ability to bind to the mariner repeat elements in the genome.^{[12][13][14][15]} SETMAR has been found to affect the expression and splicing of genes close to or containing mariner repeat elements via its functions in histone methylation.^[12][13][15] Both the SET, via its methyltransferase activity,^[7][8][16] and the mariner, with its DNA-binding ^[17] and nuclease activities,^{[18][19][20][21][16]} domains of SETMAR have been shown to act in non-homologous end joining (NHEJ) to repair DNA double strand breaks.