| The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. | |
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MedLine Citation:
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PMID: 11555648 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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S-phase onset is controlled, so that it occurs only once every cell cycle. DNA is licensed for replication after mitosis in G(1), and passage through S-phase removes the license to replicate. In fission yeast, Cdc6/18 and Cdt1, two factors required for licensing, are central to ensuring that replication occurs once per cell cycle. We show that the human Cdt1 homologue (hCdt1), a nuclear protein, is present only during G(1). After S-phase onset, hCdt1 levels decrease, and it is hardly detected in cells in early S-phase or G(2). hCdt1 can associate with the DNA replication inhibitor Geminin, however these two proteins are mostly expressed at different cell cycle stages. hCdt1 mRNA, in contrast to hCdt1 protein, is expressed in S-phase-arrested cells, and its levels do not change dramatically during a cell cycle, suggesting that proteolytic rather than transcriptional controls ensure the timely accumulation of hCdt1. Consistent with this view, proteasome inhibitors stabilize hCdt1 in S-phase. In contrast, hCdc6/18 levels are constant through most of the cell cycle and are only low for a brief period at the end of mitosis. These results suggest that the presence of active hCdt1 may be crucial for determining when licensing is legitimate in human cells. |
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Authors:
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H Nishitani; S Taraviras; Z Lygerou; T Nishimoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2001-09-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 276 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2001 Nov |
Date Detail:
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Created Date: 2001-11-23 Completed Date: 2002-01-10 Revised Date: 2013-01-01 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 44905-11 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. hideon@molbiol.med.kyushu-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Blotting, Western COS Cells Cell Cycle Cell Cycle Proteins / chemistry*, metabolism*, pharmacology Cell Line Cell Nucleus / metabolism Cloning, Molecular DNA / biosynthesis* DNA-Binding Proteins / chemistry*, metabolism* G1 Phase* HeLa Cells Humans Microscopy, Fluorescence Plasmids / metabolism Precipitin Tests RNA, Messenger / metabolism S Phase* Time Factors Tissue Distribution Transcription, Genetic Xenopus Xenopus Proteins |
| Chemical | |
Reg. No./Substance:
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0/CDT1 protein, human; 0/Cdt1 protein, Xenopus; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/GMNN protein, Xenopus; 0/GMNN protein, human; 0/RNA, Messenger; 0/Xenopus Proteins; 9007-49-2/DNA |
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