Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene. [3] [4] [5] [6]
Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene. [3] [4] [5] [6]
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.