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Science 17 December 1993: Vol. 262. no. 5141, pp. 1838 - 1844 DOI: 10.1126/science.8266071
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Articles
Science, Vol 262, Issue 5141, 1838-1844
Copyright © 1993 by American Association for the Advancement of Science
Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae
M Foss,
FJ McNally,
P Laurenson,
and
J Rine
Department of Molecular and Cellular Biology, University of California, Berkeley 94720.
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.
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