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

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.

[1]  S. Bell,et al.  Yeast origin recognition complex functions in transcription silencing and DNA replication. , 1993, Science.

[2]  J. Diffley,et al.  Protein-DNA interactions at a yeast replication origin , 1992, Nature.

[3]  Bruce Stillman,et al.  ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex , 1992, Nature.

[4]  J. Rine,et al.  An origin of DNA replication and a transcription silencer require a common element. , 1992, Science.

[5]  A. Klar,et al.  Active genes in budding yeast display enhanced in vivo accessibility to foreign DNA methylases: a novel in vivo probe for chromatin structure of yeast. , 1992, Genes & development.

[6]  J. Rine,et al.  A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[7]  C. Newlon,et al.  Evidence suggesting that the ARS elements associated with silencers of the yeast mating-type locus HML do not function as chromosomal DNA replication origins , 1991, Molecular and cellular biology.

[8]  D. Shore,et al.  Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Clarke,et al.  The Saccharomyces cerevisiae STE14 gene encodes a methyltransferase that mediates C‐terminal methylation of a‐factor and RAS proteins. , 1991, The EMBO journal.

[10]  D. Shore,et al.  RAP1 protein activates and silences transcription of mating-type genes in yeast , 1991 .

[11]  J. Szostak,et al.  Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML. , 1990, Molecular and cellular biology.

[12]  M. Grunstein,et al.  Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. Kornberg,et al.  A yeast ARS-binding protein activates transcription synergistically in combination with other weak activating factors , 1990, Molecular and cellular biology.

[14]  B. Morgan,et al.  Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. , 1990, Science.

[15]  F. Spencer,et al.  Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. , 1990, Genetics.

[16]  H. Berg.  Cold Spring Harbor Symposia on Quantitative Biology.: Vol. LII. Evolution of Catalytic Functions. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1987, ISBN 0-87969-054-2, xix + 955 pp., US $150.00. , 1989 .

[17]  S. Shuman,et al.  Mapping the active-site tyrosine of vaccinia virus DNA topoisomerase I. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Sternglanz,et al.  Mapping of the active site tyrosine of eukaryotic DNA topoisomerase I. , 1989, The Journal of biological chemistry.

[19]  J. Wang,et al.  Peptide sequencing and site-directed mutagenesis identify tyrosine-727 as the active site tyrosine of Saccharomyces cerevisiae DNA topoisomerase I. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Sikorski,et al.  A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. , 1989, Genetics.

[21]  M. Grunstein,et al.  Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast , 1988, Cell.

[22]  C. Newlon,et al.  Close association of a DNA replication origin and an ARS element on chromosome III of the yeast, Saccharomyces cerevisiae. , 1988, Nucleic acids research.

[23]  K. Nasmyth,et al.  A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation , 1987, Cell.

[24]  Kim Nasmyth,et al.  Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements , 1987, Cell.

[25]  W. L. Fangman,et al.  The localization of replication origins on ARS plasmids in S. cerevisiae , 1987, Cell.

[26]  D. Botstein,et al.  A Tn10-lacZ-kanR-URA3 gene fusion transposon for insertion mutagenesis and fusion analysis of yeast and bacterial genes. , 1987, Genetics.

[27]  I. Herskowitz,et al.  Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. , 1987, Genetics.

[28]  L. Breeden,et al.  Characterization of a “silencer” in yeast: A DNA sequence with properties opposite to those of a transcriptional enhancer , 1985, Cell.

[29]  Ronald W. Davis,et al.  Mitotic stability of yeast chromosomes: A colony color assay that measures nondisjunction and chromosome loss , 1985, Cell.

[30]  L. Hartwell,et al.  Genetic analysis of the mitotic transmission of minichromosomes , 1985, Cell.

[31]  Thomas A. Kunkel,et al.  Rapid and efficient site-specific mutagenesis without phenotypic selection. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[32]  K. Nasmyth,et al.  Role of DNA replication in the repression of silent mating type loci in yeast , 1984, Nature.

[33]  J. Broach,et al.  Identification of sites required for repression of a silent mating type locus in yeast. , 1984, Journal of molecular biology.

[34]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[35]  U. Schibler,et al.  Changes in size and secondary structure of the ribosomal transcription unit during vertebrate evolution. , 1975, Journal of molecular biology.