Suggested that DNA dependent protein kinase was a cellular element involved in gaprepair, and then ataxia telangiectasia mutated, ataxia telangiectasia and Rad3 connected, Nijmegen pan HDAC inhibitor breakage syndrome 1, and poly polymerase 1 are also nominated as cellular proteins involved in efficient viral transduction. Using KU55933, a particular ATM inhibitor, Lau et al. proposed that ATM can be involved with HIV 1 transduction, although Sakurai et al. shown that DNA damage repair enzymes take part in multiple ways of retroviral infection. These findings support the value of DNA double strand breaks in viral transduction, even though their roles are controversial. A possible explanation for discrepancies in reported observations is the fact that the single-strand breaks are repaired in an obsolete manner by DNA damage repair minerals, the appearance of which varies among cells. It is also possible that DSBs have modest effects on viral transduction, which may be overwhelmed by the infectivity Nucleophilic aromatic substitution of the wild type virus. . This means it is important to evaluate the ramifications of DSBs using more advanced experimental methods. Here we focused on the part of DNA damage, particularly in integration of viral DNA. Interestingly, HIV 1 DNA built-into artificially induced DSBs in a IN CA independent way and DNA damaging agents up-regulated the irritation of IN CA defective virus. The results of DSBs on viral integration were immune to raltegravir, an IN CA chemical. Furthermore, Vpr, an accessory gene product of HIV 1, mimicked DNA damaging agents and improved INCA separate viral transduction in to macrophages. Contagious secondary virus was generated without any variations that produced phenotypes resistant to RAL, even when the catalytic activity of IN was damaged. Based on these findings, we suggest that the ATM dependent deubiquitinating enzyme inhibitor function of DSB unique integration of viral DNA and the Vpr induced DSBs are novel targets for anti HIV substances that inhibit viral transduction into MDMs, a continual reservoir of HIV 1 infection. Benefits HIV 1 integrates into the websites of artificially induced DSBs To know the tasks of DSBs in integration of viral DNA into macrophages, we established a method using THP 1 cells, a human monocytic leukemia cell line that separates into macrophage like cells after-treatment with phorbol myristate acetate. We transfected THP 1 cells with plasmid DNA that included the recognition sequence for I SceI, a rarecutting endonuclease and received clones with the I SceI site after drug choice. Using the experimental methods outlined in Figure 1A, the frequency of viral DNA integration in to I SceI web sites was assessed. After PMA treated cells were infected with VSVG pseudotyped WT virus Page1=46) together with adenovirusexpressing I SceI, provirus DNA was detected in the I SceI provirus site or its vicinity.