Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae

• Published in: Science (American Association for the Advancement of Science) 1993-12, Vol.262 (5141), p.1838-1844
• Main Authors: Foss, M, McNally, F.J, Laurenson, P, Rine, J
• Format: Article
• Language: English
• Subjects: ADN; Alleles; Amino Acid Sequence; Biological and medical sciences; Cell Cycle; Chromosome replication; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; Daughter cells; Diploidy; DNA Replication; DNA, Fungal - genetics; DNA, Fungal - metabolism; DNA-Binding Proteins; Fundamental and applied biological sciences. Psychology; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; GENE; Gene Expression Regulation, Fungal; GENES; Genes, Fungal; Genetic aspects; Genetic loci; Genetic mutation; Genetic regulation; Genetic transcription; Genetics of eukaryotes. Biological and molecular evolution; Molecular Sequence Data; Mutation; Origin Recognition Complex; Phenotype; Phenotypes; Plasmids; Regulation; Replicon; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Saccharomyces; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Silencers; Thallophyta, bryophyta; Transcription (Genetics); Transcription, Genetic; Vegetals
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8266071

In Saccharomyces cerevisiae, the HMR-E silencer blocks site-specific interactions between proteins and their recognition sequences in the vicinity of the silencer. Silencer function is correlated with the firing of an origin of replication at HMR-E. An essential gene with a role in transcriptional silencing was identified by means of a screen for mutations affecting expression of HMR. This gene, known as ORC2, was shown to encode a component of the origin recognition complex that binds yeast origins of replication. A temperature-sensitive mutation in ORC2 disrupted silencing in cells grown at the permissive temperature. At the restrictive temperature, the orc2-1 mutation caused cell cycle arrest at a point in the cell cycle indicative of blocks in DNA replication. The orc2-1 mutation also resulted in the enhanced mitotic loss of a plasmid, suggestive of a defect in replication. These results provide strong evidence for an in vivo role of ORC in both chromosomal replication and silencing, and provide a link between the mechanism of silencing and DNA replication