Cloning and characterization of two mouse genes with homology to the yeast Sir2 gene.

The yeast Sir2 gene encodes a protein (Sir2p) that plays an essential role in silencing regulation at mating-type loci, rDNA, and telomeres. Recent studies have also shown that the protein participates in cell cycle regulation, DNA double-strand break repair, meiotic checkpoint control, and histone deacetylation. Overexpression of wildtype Sir2p in yeast resulted in an extended life span but mutant Sir2p shortened the life span, suggesting its function in aging processes. Sir2p is evolutionarily conserved from prokaryotes to higher eukaryotes. However, its function(s) in mammals remains unknown. To investigate Sir2p function(s) in mice, we cloned and characterized two mouse Sir2-like genes. Our results revealed that the two mouse Sir2-like proteins (mSIR2L2 and mSIR2L3) are most similar to the human Sir2-like proteins SIR2L2 and SIR2L3, respectively. Sir2 core domains are highly conserved in the two proteins and yeast Sir2p; however, the intracellular localizations of both mSIR2L2 and mSIR2L3 differ from that of yeast Sir2p and from one another. The two mouse genes have completely different genomic structures but were mapped on the same chromosome. It seems that the two mouse proteins, though they have Sir2 conserved domains, may function differently than yeast Sir2p.