Metnase, also known as SETMAR, is a SET and transposase fusion protein with an 
undefined role in mammalian DNA repair. The SET domain is responsible for 
histone lysine methyltransferase activity at histone 3 K4 and K36, whereas the 
transposase domain possesses 5'-terminal inverted repeat (TIR)-specific DNA 
binding, DNA looping, and DNA cleavage activities. Although the transposase 
domain is essential for Metnase function in DNA repair, it is not clear how a 
protein with sequence-specific DNA binding activity plays a role in DNA repair. 
Here, we show that human homolog of the ScPSO4/PRP19 (hPso4) forms a stable 
complex with Metnase on both TIR and non-TIR DNA. The transposase domain 
essential for Metnase-TIR interaction is not sufficient for its interaction with 
non-TIR DNA in the presence of hPso4. In vivo, hPso4 is induced and co-localized 
with Metnase following ionizing radiation treatment. Cells treated with 
hPso4-siRNA failed to show Metnase localization at DSB sites and 
Metnase-mediated stimulation of DNA end joining coupled to genomic integration, 
suggesting that hPso4 is necessary to bring Metnase to the DSB sites for its 
function(s) in DNA repair.