ИСТИНА

The integration of the HIV DNA into the host genome is completed by cellular factors that repair the short gaps flanking the proviral DNA. We have shown earlier, that viral integrase can directly interact with Ku70 repair factor, and this interaction is weakened by E212A/L213A substitutions in integrase. The transduction of HEK 293T cells by a singleround HIV­1 vector is found to be decreased in cells stably depleted of the DNA­PK repair components (Ku70, Ku80 or DNA­PKcs). We have established a qPCR­based approach for quantitative measurement of postintegrational gap repair and shown that depletion of any DNA­PK component reduces gap­repair efficiency in our system. The same effects have been detected in presence of specific DNA­PKcs inhibitor Nu7441. Viral vector carrying E212A/L213A integrase substitutions demonstrates decreased gap­repair and a reduced sensitivity to the DNA­-PK components depletion while its integrational capacity remains at the wild­type level. We speculate that integrase recruits DNA­PK complex to gap cites and facilitates gap­repair through a direct interaction with Ku70 subunit. This work was supported by RFBR grant 17­04­ 01178 and RSF grant 17­14­1107 (development of the gap repair approach).