| Phosphorylation sites on Tyr28 and the C-terminus of Rad9 are required for inhibition of premature chromosomal condensation across the entire S phase. | |
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MedLine Citation:
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PMID: 18769057 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rad9 is required for the activity of the genotoxin-induced checkpoint signaling pathway to control cell cycle progress and maintain genomic stability. In the fission yeast S. Pombe and chicken cells, the Rad9 gene is essential for prevention of premature chromosomal condensation (PCC:S/M checkpoint control). However, precise features in the S/M checkpoint controlled by Rad9 in mammalian cells are still not clear. In this study, mouse embryonic stem (ES) cells with a targeted deletion of Mrad9, the counterpart of S. pombe rad9, were used to evaluate the detailed function of Mrad9 in S/M checkpoint control. We found that Mrad9 deletion from ES cells led to failure of S/M checkpoint control across the entire S phase, and was alleviated by introducing mouse or human Rad9 into the Mrad9-deleted cells. We also found that the phosphorylation sites on Tyr28 and the C-terminus of Rad9 are required for this checkpoint control. Moreover, the DNA replication inhibitor hydroxyurea (HU) induced cdc2 Tyr15 phosphorylation and increased 14-3-3sigma protein levels in Mrad9(+)/(+) ES cells, but failed to do so in Mrad9(-)/(-) ES cells. Taken together, these results suggest that phosphorylation of Rad9 plays a critical role in the activation of the S/M checkpoint, and that downstream proteins cdc2 and 14-3-3sigma mediate this function. |
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Authors:
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Chunbo Zhang; Charles Xia Zhang; Yikun He; Haiying Hang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-25 |
Journal Detail:
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Title: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Volume: 22 ISSN: 1421-9778 ISO Abbreviation: Cell. Physiol. Biochem. Publication Date: 2008 |
Date Detail:
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Created Date: 2008-09-04 Completed Date: 2008-11-17 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9113221 Medline TA: Cell Physiol Biochem Country: Switzerland |
Other Details:
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Languages: eng Pagination: 295-306 Citation Subset: IM |
Copyright Information:
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Copyright 2008 S. Karger AG, Basel. |
Affiliation:
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National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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14-3-3 Proteins
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metabolism Amino Acid Sequence Animals CDC2 Protein Kinase / metabolism Cell Cycle Proteins / chemistry*, metabolism* Chromosomes, Mammalian / drug effects, metabolism* Cycloheximide / pharmacology Embryonic Stem Cells / cytology, drug effects, metabolism G1 Phase / drug effects Gene Deletion Hydroxyurea / pharmacology Mice Mitosis / drug effects Molecular Sequence Data Phosphoserine / metabolism Phosphotyrosine / metabolism* S Phase* / drug effects Structure-Activity Relationship Time Factors |
| Chemical | |
Reg. No./Substance:
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0/14-3-3 Proteins; 0/Cell Cycle Proteins; 127-07-1/Hydroxyurea; 139691-42-2/rad9 protein; 17885-08-4/Phosphoserine; 21820-51-9/Phosphotyrosine; 66-81-9/Cycloheximide; EC 2.7.11.22/CDC2 Protein Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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