Fig. 9
From: Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response
Hypothetical model of DDR and DSB induction by Vpr. Vpr unwinds dsDNA and allows limited loading of RPA70. Simultaneously, Vpr induces ubiquitination of histone H2B, and histone eviction occurs in the vicinity. Chromatin remodeling by histone eviction promotes efficient loading of RPA70, leading to G2/M checkpoint activation by ATR (left side). Vpr-induced unwinding of dsDNA in turn causes accumulation of supercoiling of DNA and formation of Topo1-cc (right side). In conjunction with DNA replication or transcription, Topo1-cc induces DSB formation, and proviral DNA is integrated at the DSB sites