SIRT7

SIRT7 is a mammalian sirtuin and NAD⁺-dependent histone/protein deacetylase involved in genome stability, metabolism, stress responses, tumorigenesis, ribosome biogenesis, and transcriptional regulation^[1]. Mechanistically, DNA activates SIRT7 to deacetylate histone H3 in chromatin, and RNA increases SIRT7 catalytic efficiency while ribosomal RNA acts as a predominant binding partner^[1][2]. Therefore, SIRT7 connects nucleolar biology with chromatin regulation through deacetylation of fibrillarin, maintenance of H2AQ104 methylation, and support of cell-cycle-dependent rDNA transcription^[3]. SIRT7 also deacetylates ribosomal RNA ac4C, indicating an epitranscriptional role in rRNA modification and aging-related regulation^[4]. In DNA damage models, SIRT7 promotes genome integrity by PARP1-dependent recruitment to DNA damage sites, H3K18Ac modulation, 53BP1 recruitment, and non-homologous end joining repair^[5]. In cellular senescence models, SIRT7 supports SNF2H association with rDNA sequences and protects against rDNA instability, rDNA copy loss, and acute senescence^[6]. Compared with SIRT6, SIRT7 shows a distinct activation mechanism because DNA activates SIRT7 peptide deacetylation, whereas SIRT6 peptide deacetylation is not DNA-activated^[1]. For experimental applications, improved DNA- or RNA-activated enzymatic assays and SIRT7 lysine deacylase profiling support development of SIRT7 modulators^[1][2][7].