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Sir1 protein, one of four Sir proteins needed for assembly of silenced chromatin domains in Saccharomyces cerevisiae, and its role in silencing HMR, a cryptic mating-type locus are discussed. Sir1p was in very low concentrations in yeast cells but associated with HMR at all cell cycle states seen. Mechanisms that set up and inhibit assembly of silenced chromatin to a few discrete chromosomal domains and the origin recognition complex have been investigated.

Research reveals that like in mammalian cells, budding yeast deploys heterochromatic silencing proteins, such as Sir1, to attract the histone deposition factor toward centromeric chromatin. However, the two cell types use different mechanisms for the process. Data indicate that Sir1 contributes to mitotic chromosome stability as well.

Silencing of the cryptic mating-type loci HMR and HML requires the recognition of DNA sequence elements called silencers by the Sir1p, one of four proteins dedicated to the assembly of silenced chromatin in Saccharomyces cerevisiae. The Sir1p is thought to recognize silencers indirectly through interactions with proteins that hind the silencer DNA directly, such as the origin recognition complex (ORC). Eight recessive alleles of SIR1 were discovered that encode mutant Sir1 proteins specifically defective in their ability to recognize the HMR-E silencer. The eight missense mutations all map within a 17-amino-acid segment of Sir1p, and this segment was also required for Sir1p's interaction with Orc1p. The mutant Sir1 proteins could function in silencing if tethered to a silencer directly through a heterologous DNA-binding domain. Thus the amino acids identified are required for Sir1 protein's recognition of the HMR-E silencer and interaction with Orc1p, but not for its ability to function in silencing per se. The approach used to find these mutations may be applicable to defining interaction surfaces on proteins involved in other processes that require the assembly of macromolecular complexes.