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 γ-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.
We recently identified a Transposase domain protein called Metnase, which assists in repairing DNA double-strand breaks (DSB) via non-homologous end-joining (NHEJ), and is important for foreign DNA integration into a host cell genome. Since integration is essential for productive lentiviral infection we examined whether Metnase expression levels could have an influence on lentiviral genomic integration. Using cells stably transduced to either over-or under-express Metnase we determined that the expression level of Metnase did indeed correlate with live lentiviral integration. Changes in Metnase levels were accompanied by changes in the number of copies of integrated lentiviral cDNA. While Metnase levels affected lentiviral integration, it had no effect on the amount of either total cellular viral RNA, cDNA or 2-LTR circles. Therefore, Metnase enhances the integration of lentivirus DNA into the host cell genome.
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