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

摘要: Human papillomaviruses (HPV) regulate their differentiation-dependent life cycles by activating a number of cellular pathways, such as the DNA damage response, through control post-translational protein modification. Sirtuin 1 (SIRT1) is deacetylase that modulates acetylation substrates, resulting in activation pathways controlling gene expression and repair. Our studies indicate SIRT1 levels are increased cells containing episomes high-risk HPV types combined action E6 E7 oncoproteins. Knockdown these with shRNAs impairs viral activities including genome maintenance, amplification late transcription, minimal effects on proliferation ability. Abrogation was also seen following treatment inhibitor, EX-527. Importantly, binds multiple regions undifferentiated cells, but this association lost upon differentiation. regulates Histone H1 (Lys26) H4 (Lys16) bound to genomes may contribute regulation replication expression. The HPVs requires factors Ataxia Telangiectasia Mutated (ATM) pathway recruitment both NBS1 Rad51 genomes. These observations demonstrate critical regulator aspects cycle.