Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration.
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.
Williamson
Elizabeth A
EA
Department of Hematology-Oncology, Cancer Research and Treatment Center, Department of Medicine, 900 Camino de Salud, University of New Mexico Health Science Center, Albuquerque, NM 87131, United States. ewilliamson@salud.unm.edu
Farrington
Jacqueline
J
Martinez
Leah
L
Ness
Scott
S
O'Rourke
John
J
Lee
Suk-Hee
SH
Nickoloff
Jac
J
Hromas
Robert
R
D002460:Cell Line; D004260:DNA Repair / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism*
D011495:Histone-Lysine N-Methyltransferase