SIRT7 (sirtuin 7; HGNC:14935, NCBI Gene ID 51547) is a human locus mapped to chromosome band 17q25.3 that encodes nucleolar & nuclear chromatin NAD+-dependent deacetylase/desuccinylase Sirtuin 7 (400 aa; EC 2.3.1.286). SIRT7 acts in selective Histone H3 Lys18 (H3K18ac) & Lys36 deacetylation, nucleolar rDNA heterochromatin stability, 53BP1 NHEJ repair & GABP-beta1 mitochondrial homeostasis, together with SIRT6 (Partner Chromatin DNA-Repair Sirtuin Gene), SIRT1 (Nuclear Sirtuin 1 Paralog Gene), and NRF1 (Recruits SIRT7 to Mitochondrial Ribosomal Promoters). Encodes the nucleolar and chromatin-associated sirtuin 7 that deacetylates H3K18ac, stabilizes ribosomal DNA repeats, and promotes DNA repair.
Protects hematopoietic stem cells from mitochondrial unfolded protein stress & suppresses oncogenic H3K18ac hypoacetylation/rDNA instability
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 10-exon gene near the telomere of chromosome 17q25.3 encoding a 400-amino-acid enzyme with an arginine-rich N-terminal nucleolar localization domain and a catalytic core whose deacetylase and desuccinylase activity is dramatically stimulated upon binding double-stranded DNA, nucleosomes, and ribosomal/transfer RNAs (rRNA and tRNA).
Cellular & Tissue Expression Profile: Concentrated inside the nucleolus (associated with RNA Polymerase I and rDNA tandem repeats) and nuclear euchromatin/heterochromatin of proliferating cells, hematopoietic stem cells, hepatocytes, and cardiomyocytes.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Exhibits exquisite substrate specificity for Histone H3 acetylated at Lys18 (H3K18ac) and Lys36 (H3K36ac) as well as H3K122 succinylation: at DNA double-strand breaks, ATM-recruited SIRT7 deacetylates H3K18ac to promote 53BP1 focal recruitment and non-homologous end joining; in the nucleolus, SIRT7 recruits DNMT1 and SIRT1 to silence excess ribosomal DNA (rDNA) copy instability and prevent toxic extrachromosomal rDNA circle formation; and in hepatic and hematopoietic stem cells, SIRT7 deacetylates GABP-beta1 (NRF2 beta subunit) and complexes with NRF1 to balance mitochondrial ribosomal protein expression and prevent the mitochondrial unfolded protein response (UPRmt).
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Sirt7-deficient mice develop premature aging phenotypes including kyphosis, loss of subcutaneous fat, hepatic microvesicular steatosis, inflammatory cardiomyopathy, and hematopoietic stem cell exhaustion driven by rDNA instability and mitochondrial folding stress.
Therapeutic & Clinical Pharmacology: Studied alongside SIRT1 and SIRT6 as a guardian of nucleolar chromatin architecture, stem cell regenerative capacity, and genomic stability during chronological aging.