Yeast origin recognition complex is involved in DNA replication and transcriptional silencing

The HMR E silencer represses transcription of silent mating-type genes in the budding yeast Saccharomyces cerevisiae and contains three redundant regulatory elements A, E and B (ref. 1). The A element contains the 11 base pair consensus sequence that is essential for the firing of DNA replication origins. A multisubunit protein called the origin recognition complex (ORC) binds specifically to this consensus sequence within yeast origins in vitro and in vivo. We isolated mutants in A element-mediated silencing and report here that one of the genes we identified, RRR1, encodes ORC2, the 72K subunit of ORC. RRR1/ORC2 is an essential gene, but the rrr1-316 allele, which is viable, is defective in the replication of nuclear DNA and the maintenance of the 2-microns episomal DNA. This is, to our knowledge, the first genetic evidence that ORC is involved in DNA replication and silencing.