Transposase domain proteins mediate DNA movement from one location in the genome 
to another in lower organisms. However, in human cells such DNA mobility would 
be deleterious, and therefore the vast majority of transposase-related sequences 
in humans are pseudogenes. We recently isolated and characterized a SET and 
transposase domain protein termed Metnase that promotes DNA double-strand break 
(DSB) repair by non-homologous end-joining (NHEJ). Both the SET and transposase 
domain were required for its NHEJ activity. In this study we found that Metnase 
interacts with DNA Ligase IV, an important component of the classical NHEJ 
pathway. We investigated whether Metnase had structural requirements of the free 
DNA ends for NHEJ repair, and found that Metnase assists in joining all types of 
free DNA ends equally well. Metnase also prevents long deletions from processing 
of the free DNA ends, and improves the accuracy of NHEJ. Metnase levels 
correlate with the speed of disappearance of gamma-H2Ax sites after ionizing 
radiation. However, Metnase has little effect on homologous recombination repair 
of a single DSB. Altogether, these results fit a model where Metnase plays a 
role in the fate of free DNA ends during NHEJ repair of DSBs.