A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span

Control of chromosome structure is important in the regulation of gene expression, recombination, DNA repair, and chromosome stability. In a two-hybrid screen for proteins that interact with the Drosophila CREB-binding protein (dCBP), a known histone acetyltransferase and transcriptional coactivator, we identified the Drosophila homolog of a yeast chromatin regulator, Sir2. In yeast, Sir2 silences genes via an intrinsic NAD(+)-dependent histone deacetylase activity. In addition, Sir2 promotes longevity in yeast and in Caenorhabditis elegans. In this report, we characterize the Drosophila Sir2 (dSir2) gene and its product and describe the generation of dSir2 amorphic alleles. We found that dSir2 expression is developmentally regulated and that dSir2 has an intrinsic NAD(+)-dependent histone deacetylase activity. The dSir2 mutants are viable, fertile, and recessive suppressors of position-effect variegation (PEV), indicating that, as in yeast, dSir2 is not an essential function for viability and is a regulator of heterochromatin formation and/or function. However, mutations in dSir2 do not shorten life span as predicted from studies in yeast and worms.