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Genetics, Vol. 167, 579-591, June 2004, Copyright © 2004
doi:10.1534/genetics.103.024851

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The Origin Recognition Complex Links Replication, Sister Chromatid Cohesion and Transcriptional Silencing in Saccharomyces cerevisiae

Bernhard Suter*, Amy Tong{dagger}, Michael Chang{ddagger}, Lisa Yu{ddagger}, Grant W. Brown{ddagger}, Charles Boone{dagger} and Jasper Rine*,1

* Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202
{dagger} Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
{ddagger} Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada

1 Corresponding author: Department of Molecular and Cell Biology, University of California, 522 Barker Hall #3202, Berkeley, CA 94720-3202.
E-mail: jrine{at}uclink.berkeley.edu

Mutations in genes encoding the origin recognition complex (ORC) of Saccharomyces cerevisiae affect initiation of DNA replication and transcriptional repression at the silent mating-type loci. To explore the function of ORC in more detail, a screen for genetic interactions was undertaken using large-scale synthetic lethal analysis. Combination of orc2-1 and orc5-1 alleles with the complete set of haploid deletion mutants revealed synthetic lethal/sick phenotypes with genes involved in DNA replication, chromatin structure, checkpoints, DNA repair and recombination, and other genes that were unexpected on the basis of previous studies of ORC. Many of these genetic interactions are shared with other genes that are involved in initiation of DNA replication. Strong synthetic interactions were demonstrated with null mutations in genes that contribute to sister chromatid cohesion. A genetic interaction between orc5-1 and the cohesin mutant scc1-73 suggested that ORC function contributes to sister chromatid cohesion. Thus, comprehensive screening for genetic interactions with a replication gene revealed a connection between initiation of DNA replication and sister chromatid cohesion. Further experiments linked sister chromatid cohesion genes to silencing at mating-type loci and telomeres.




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