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. 2018 Jan 16;15:8. doi: 10.1186/s12977-018-0391-8

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© The Author(s) 2018

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 9 — 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