Post-Integrational DNA Repair of HIV-1 Is Associated with the Activation of DNA-PK and ATM Cellular Protein Kinases and Phosphorylation of Their Targets

Integration of the DNA copy of the HIV-1 genome into the cellular genome results in series of damages, the repair of which is critical for successful viral replication. We have previously demonstrated that the ATM and DNA-PK kinases, normally responsible for repairing double-strand breaks in the cellular DNA, are required to initiate HIV-1 post-integration repair, even though integration does not result in double-strand DNA breaks. In this study, we analyzed changes in the phosphorylation status of ATM (pSer1981), DNA-PK (pSer2056) and their related kinase ATR (pSer428), as well as their targets: Chk1 (pSer345), Chk2 (pThr68), H2AX (pSer139) and p53 (pSer15) during HIV-1 post-integration repair. We have shown that ATM and DNA-PK, but not ATR, undergo autophosphorylation during postintegration DNA repair and phosphorylate their target proteins Chk2 and H2AX. These data indicate common signaling mechanisms between double-strand DNA break repair and postintegration repair of HIV-1.