| Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. | |
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MedLine Citation:
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PMID: 16716188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chromosomal replication initiates through the assembly of a prereplicative complex (pre-RC) at individual replication origins in the G1-phase, followed by activation of these complexes in the S-phase. In Saccharomyces cerevisiae, the origin recognition complex (ORC) binds replication origins throughout the cell cycle and participates in pre-RC assembly. Whether the ORC plays an additional role subsequent to pre-RC assembly in replication initiation or any other essential cell cycle process is not clear. To study the function of the ORC during defined cell cycle periods, we performed cell cycle execution point analyses with strains containing a conditional mutation in the ORC1, ORC2 or ORC5 subunit of ORC. We found that the ORC is essential for replication initiation, but is dispensable for replication elongation or later cell cycle events. Defective initiation in ORC mutant cells results in incomplete replication and mitotic arrest enforced by the DNA damage and spindle assembly checkpoint pathways. The involvement of the spindle assembly checkpoint implies a defect in kinetochore-spindle attachment or sister chromatid cohesion due to incomplete replication and/or DNA damage. Remarkably, under semipermissive conditions for ORC1 function, the spindle checkpoint alone suffices to block proliferation, suggesting this checkpoint is highly sensitive to replication initiation defects. We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions. |
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Authors:
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Daniel G Gibson; Stephen P Bell; Oscar M Aparicio |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes to cells : devoted to molecular & cellular mechanisms Volume: 11 ISSN: 1356-9597 ISO Abbreviation: Genes Cells Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-23 Completed Date: 2006-09-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9607379 Medline TA: Genes Cells Country: England |
Other Details:
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Languages: eng Pagination: 557-73 Citation Subset: IM |
Affiliation:
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Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2910, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Cell Cycle / physiology* Cell Cycle Proteins / genetics, metabolism DNA Damage / genetics DNA, Fungal / metabolism Gene Silencing Mitosis Mitotic Spindle Apparatus / genetics, metabolism Mutation Origin Recognition Complex / genetics*, metabolism* Protein Subunits Protein-Serine-Threonine Kinases / genetics, metabolism Saccharomyces cerevisiae / cytology*, genetics Saccharomyces cerevisiae Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GM52339/GM/NIGMS NIH HHS; GM65494/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/DNA, Fungal; 0/Origin Recognition Complex; 0/Protein Subunits; 0/Saccharomyces cerevisiae Proteins; 139691-42-2/rad9 protein; EC 2.7.1.-/RAD53 protein, S cerevisiae; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
| Comments/Corrections | |
Erratum In:
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Genes Cells. 2006 Aug;11(8):969 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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