Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2.

The proteins encoded by the SIR1, SIR2, SIR3 and SIR4 genes in yeast repress transcription at the mating type loci and telomeres. Among the SIR genes, SIR2 is the most evolutionarily conserved, and a number of genes with homology to SIR2 have been identified. In addition to transcriptional silencing, the product of SIR2 gene (Sir2p) has been shown to be involved in DNA repair and suppression of rDNA recombination. In the present study, the complete sequence of a human gene, SIR2L, with homology to the yeast SIR2 gene is presented. Comparison of the predicted sequence of the protein encoded by the SIR2L gene (SIR2Lp) with Sir2p or other proteins with homology to Sir2p reveals 20-33% overall identity and four highly conserved regions, the significance of which is unknown. SIR2L codes for a 2.1kb transcript which is expressed in various human tissues. The expression level of the transcript is found to be relatively high in the heart, brain and skeletal muscle tissues and low in lung and placenta. The intracellular location of SIR2Lp was visualized by fusion to the Green Fluorescent Protein or with a FLAG-tag. The results indicate that unlike Sir2p in yeast, SIR2Lp in human cells is found primarily in the cytoplasm. Using a mammalian inducible expression system, we also observed that unlike SIR2 in yeast, overexpression of SIR2L in human cancer cells has no effect on cell growth. Thus, although the human SIR2L gene appears to be related to the yeast SIR2 gene, it does not appear to have similar functions.