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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 15
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pubmed:dateCreated |
2006-7-26
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pubmed:abstractText |
The activity of human Cdt1 is negatively regulated by multiple mechanisms. This suggests that Cdt1 deregulation may have a deleterious effect. Indeed, it has been suggested that overexpression of Cdt1 can induce rereplication in cancer cells and that rereplication activates Ataxia-telangiectasia-mutated (ATM) kinase and/or ATM- and Rad3-related (ATR) kinase-dependent checkpoint pathways. In this report, we highlight a new and interesting aspect of Cdt1 deregulation: data from several different systems all strongly indicate that unregulated Cdt1 overexpression at pathophysiological levels can induce chromosomal damage other than rereplication in non-transformed cells. The most important finding in these studies is that deregulated Cdt1 induces chromosomal damage and activation of the ATM-Chk2 DNA damage checkpoint pathway even in quiescent cells. These Cdt1 activities are negatively regulated by cyclin A/Cdks, probably through modification by phosphorylation. Furthermore, we found that deregulated Cdt1 induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this would be a new molecular mechanism leading to carcinogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Origin Recognition Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...,
http://linkedlifedata.com/resource/pubmed/chemical/checkpoint kinase 2
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9533
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
119
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3128-40
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:16835273-Animals,
pubmed-meshheading:16835273-Cell Cycle,
pubmed-meshheading:16835273-Cell Cycle Proteins,
pubmed-meshheading:16835273-Cell Line, Tumor,
pubmed-meshheading:16835273-Chromosomal Instability,
pubmed-meshheading:16835273-Chromosomes,
pubmed-meshheading:16835273-DNA Damage,
pubmed-meshheading:16835273-DNA Replication,
pubmed-meshheading:16835273-DNA-Binding Proteins,
pubmed-meshheading:16835273-Enzyme Activation,
pubmed-meshheading:16835273-Fibroblasts,
pubmed-meshheading:16835273-Humans,
pubmed-meshheading:16835273-Karyotyping,
pubmed-meshheading:16835273-Nuclear Proteins,
pubmed-meshheading:16835273-Origin Recognition Complex,
pubmed-meshheading:16835273-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16835273-Rats,
pubmed-meshheading:16835273-Tumor Suppressor Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability.
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pubmed:affiliation |
Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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