SIRT3, a human SIR2 homologue, is an NAD- dependent deacetylase localized to mitochondria

AUTOR(ES)

Onyango, Patrick

FONTE

The National Academy of Sciences

RESUMO

The SIR2 (silent information regulator 2) gene family has diverse functions in yeast including gene silencing, DNA repair, cell-cycle progression, and chromosome fidelity in meiosis and aging. Human homologues, termed sirtuins, are highly conserved but are of unknown function. We previously identified a large imprinted gene domain on 11p15.5 and investigated the 11p15.5 sirtuin SIRT3. Although this gene was not imprinted, we found that it is localized to mitochondria, with a mitochondrial targeting signal within a unique N-terminal peptide sequence. The encoded protein was found also to possess NAD+-dependent histone deacetylase activity. These results suggest a previously unrecognized organelle for sirtuin function and that the role of SIRT3 in mitochondria involves protein deacetylation.

Documentos Relacionados

• A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei
• A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family
• The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
• The NAD+-dependent Sir2p histone deacetylase is a negative regulator of chromosomal DNA replication
• The Conserved Core of a Human SIR2 Homologue Functions in Yeast Silencing