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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1999-7-20
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pubmed:abstractText |
MCM proteins are a conserved family of eukaryotic replication factors implicated in the initiation of DNA replication and in the discrimination between replicated and unreplicated chromatin. However, most mcm mutants in yeast arrest the cell cycle after bulk DNA synthesis has occurred. We investigated the basis for this late S phase arrest by analyzing the effects of a temperature-sensitive mutation in fission yeast cdc19(+ )(mcm2(+)). cdc19-P1 cells show a dramatic loss of viability at the restrictive temperature, which is not typical of all S phase mutants. The cdc19-P1 cell cycle arrest requires an intact damage-response checkpoint and is accompanied by increased rates of chromosome loss and mitotic recombination. Chromosomes from cdc19-P1 cells migrate aberrantly in pulsed-field gels, typical of strains arrested with unresolved replication intermediates. The cdc19-P1 mutation reduces the level of the Cdc19 protein at all temperatures. We compared the effects of disruptions of cdc19(+ )(mcm2(+)), cdc21(+ )(mcm4(+)), nda4(+ )(mcm5(+)) and mis5(+ )(mcm6(+)); in all cases, the null mutants underwent delayed S phase but were unable to proceed through the cell cycle. Examination of protein levels suggests that this delayed S phase reflects limiting, but not absent, MCM proteins. Thus, reduced dosage of MCM proteins allows replication initiation, but is insufficient for completion of S phase and cell cycle progression.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cdc54 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Schizosaccharomyces pombe Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/mcm2 protein, S pombe,
http://linkedlifedata.com/resource/pubmed/chemical/mcm5 protein, S pombe,
http://linkedlifedata.com/resource/pubmed/chemical/mcm6 protein, S pombe
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9533
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
112 ( Pt 4)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
559-67
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9914167-Alleles,
pubmed-meshheading:9914167-Cell Cycle,
pubmed-meshheading:9914167-Cell Cycle Proteins,
pubmed-meshheading:9914167-Cell Division,
pubmed-meshheading:9914167-DNA Replication,
pubmed-meshheading:9914167-DNA-Binding Proteins,
pubmed-meshheading:9914167-Fungal Proteins,
pubmed-meshheading:9914167-Gene Dosage,
pubmed-meshheading:9914167-Mutation,
pubmed-meshheading:9914167-Phenotype,
pubmed-meshheading:9914167-S Phase,
pubmed-meshheading:9914167-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:9914167-Schizosaccharomyces,
pubmed-meshheading:9914167-Schizosaccharomyces pombe Proteins,
pubmed-meshheading:9914167-Temperature
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pubmed:year |
1999
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pubmed:articleTitle |
Reduced dosage of a single fission yeast MCM protein causes genetic instability and S phase delay.
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pubmed:affiliation |
Department of Biology, University of California, San Diego CA 92093, USA. forsburg@salk.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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