The Deacetylase Sirtuin 1 Regulates Human Papillomavirus Replication by Modulating Histone Acetylation and Recruitment of DNA Damage Factors NBS1 and Rad51 to Viral Genomes

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Human papillomaviruses regulate their differentiation-dependent life cycles by activating a number of cellular pathways, such as the DNA damage response, through control of post-translational protein modification. Sirtuin 1 (SIRT1) is a protein deacetylase that regulates the acetylation of a number of cellular substrates, resulting in activation of pathways involved in gene expression and DNA damage repair. We report here that SIRT1 protein levels are elevated in cells stably maintaining genomes of oncogenic HPVs and that SIRT1 knockdown impairs genome maintenance, productive replication and late gene transcription. The DNA damage sensing and repair pathways are critical for the HPV viral life cycle and members of this pathway, such as NBS1 and Rad51, are targets of SIRT1. Our studies demonstrate that SIRT1 binds the HPV genome and regulates both viral chromatin remodeling as well as binding of members of the homologous repair pathway to viral DNA. These findings demonstrate that binding of SIRT1 to the HPV genome is necessary for histone deacetylation and recruitment of DNA damage repair factors and is a critical step in the HPV life cycle.

Vyšlo v časopise: The Deacetylase Sirtuin 1 Regulates Human Papillomavirus Replication by Modulating Histone Acetylation and Recruitment of DNA Damage Factors NBS1 and Rad51 to Viral Genomes. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005181
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005181

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