Fig. 1

Conceptual model of viral integration. 1. Induction of DSB by ROS/NOS/Viral protein 2. DNA damage induces DDR (DNA damage response), ATM/ATR and P53 get activated to repair the damage. 3. HPV oncogenes deactivate the normal function of DDR molecules and DNA damage failed to be recognized. E7 degrades claspins and attenuate DNA damage checkpoints, while E6 degrades p53 and base excision repair gets suppressed so that the genomic DNA remains unrepaired and cell cycle proceeds. 4. Virus utilizes the DDR machinery for its replication which increases the availability of episomal DNA for integration. Breaks in the circular viral DNA may occur due to replication stress. 5. Virus and host genome come to a close proximity mediated by the BRD4-E2 complex. 6. Fusion between host and viral genome is accomplished either by Nonhomologous mediated end joining or homologous recombination repair pathway