Fig. 2
From: RETRACTED ARTICLE: Molecular mechanisms in progression of HPV-associated cervical carcinogenesis
Mechanism of HPV DNA integration: Induction of double strand breaks by reactive oxygen species, viral protein induces DNA damage response, following which ATR and P53 get activated to repair the damage. HPV oncogenes deactivate the normal function of DNA damage response (DDR). E7 acts on ATR and degrades claspin, inactivates Rb disrupting the cell cycle inhibitors p21, p27. E6 degrades p53 inhibiting DNA repair, degrades FAS-associated death domain protein (FADD) preventing apoptosis via Fas pathway, promotes degradation of transcriptional repressor, NFX1 and activates hTERT transcription. Virus utilizes the DDR machinery for its replication and close proximity with host genome is mediated by the Bromodomain protein 4, BRD4-E2 complex. The fusion between host and viral genome is accomplished by Nonhomologous mediated end joining (NHEJ) finally leading to integration of HPV DNA into the host genome