Chromosomal translocations are common in leukemia, but little is known about 
their mechanism. Metnase (also termed SETMAR) is a fusion of a histone methylase 
and transposase protein that arose specifically in primates. Transposases were 
thought to be extinct in primates because they would mediate deleterious DNA 
movement. In primates, Metnase interacts with DNA Ligase IV (Lig IV) and 
promotes nonhomologous end-joining (NHEJ) DNA repair. We show here that the 
primate-specific protein Metnase can also enhance NHEJ in murine cells and can 
also interact with murine Lig IV, indicating that it integrated into the 
preexisting NHEJ pathway after its development in primates. Significantly, 
expressing Metnase in murine cells significantly reduces chromosomal 
translocations. We propose that the fusion of the histone methylase SET domain 
and the transposase domain in the anthropoid lineage to form primate Metnase 
promotes accurate intrachromosomal NHEJ and thereby suppresses interchromosomal 
translocations. Metnase may have been selected for because it has a function 
opposing transposases and may thus play a key role in suppressing translocations 
that underlie oncogenicity.