Linked Life Data

16716188

Source:http://linkedlifedata.com/resource/pubmed/id/16716188

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-23
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1356-9597
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
557-73
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae.
pubmed:affiliation
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2910, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural