Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

Abstract

The DNA-PK complex is the major component of the predominant mechanism of DSB repair in humans. In addition, this complex is involved in many other processes such as DNA recombination, genome maintenance, apoptosis and transcription regulation. Several studies have linked the decrease of the DNA-PK activity with cancer initiation, due to defects in the repair. On another hand, higher DNA-PK expression and activity have been observed in various other tumor cells and have been linked with a decrease of the efficiency of anti-tumor drugs. It has also been shown that DNA-PK is critical for the integration of the HIV-1 DNA into the cell host genome and promotes replication and transcription of the virus. Targeting this complex makes therefore sense to treat these two pathologies. However, according to the status of HIV-1 replication (active versus latent replication) or to the tumor grade cells (initiation versus metastasis), the way to target this DNA-PK complex might be rather different. In this review, we discuss the importance of DNA-PK complex in two major pathologies i.e. HIV-1 infection and cancer, and the rationale use of therapies aiming to target this complex.

Keywords: Cancer; DNA-PK; DSB repair; HIV-1; Virus integration.