Papillomavirus Genomes Associate with BRD4 to Replicate at Fragile Sites in the Host Genome

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Papillomavirus cause persistent, but mostly self-limiting, infections of the host epithelium. However, a subset of oncogenic papillomaviruses is the causative agent of certain human cancers. In persistent infection the viral genomes are tethered to host chromosomes to maintain and partition the extrachromosomal viral genomes to daughter cells. However, in cancers viral DNA is often found integrated close to common fragile sites, regions prone to breakage, amplification and deletion. We show that the viral E2 and cellular BRD4 proteins are associated with fragile regions of the human genome and nucleate viral replication foci at these sites. This is a resourceful strategy for a virus that uses the host DNA damage response to amplify viral DNA. However, the outcome may be increased accidental integration of viral DNA, which in the case of the oncogenic viruses can promote carcinogenesis.

Vyšlo v časopise: Papillomavirus Genomes Associate with BRD4 to Replicate at Fragile Sites in the Host Genome. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004117
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004117

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