Positive roles of SAS2 in DNA replication and transcriptional silencing in yeast

Sas2p is a histone acetyltransferase implicated in the regulation of transcriptional silencing, and ORC is the six-subunit origin recognition complex involved in the initiation of DNA replication and the establishment of transcriptionally silent chromatin by silencers in yeast. We show here that SAS2 deletion (sas2 Delta) exacerbates the temperature sensitivity of the ORC mutants orc2-1 and orc5-1. Moreover, sas2 Delta and orc2-1 have a synthetic effect on cell cycle progression through S phase and initiation of DNA replication. These results suggest that SAS2 plays a positive role in DNA replication and cell cycle progression. We also show that sas2 Delta and orc5-1 have a synthetic effect on transcriptional silencing at the HMR locus. Moreover, we demonstrate that sas2 Delta reduces the silencing activities of silencers regardless of their locations and contexts, indicating that SAS2 plays a positive role in silencer function. In addition, we show that SAS2 is required for maintaining the structure of transcriptionally silent chromatin.