Document Detail


The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase.
MedLine Citation:
PMID:  11555648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Nishitani; S Taraviras; Z Lygerou; T Nishimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-09-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-23     Completed Date:  2002-01-10     Revised Date:  2013-01-01    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44905-11     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. hideon@molbiol.med.kyushu-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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