Source:http://linkedlifedata.com/resource/pubmed/id/11724580
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
48
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pubmed:dateCreated |
2001-11-28
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pubmed:abstractText |
Treatment of cells with the enediyne C-1027 is highly efficient at inducing single- and double-strand DNA breaks. This agent is highly cytotoxic when used at picomolar levels over a period of days. For this study, C-1027 has been used at higher levels for a much shorter time period to look at early cellular responses to DNA strand breaks. Extracts from cells treated with C-1027 for as little as 2 h are deficient in SV40 DNA replication activity. Treatment with low levels of C-1027 (1-3 nM) does not result in the presence of a replication inhibitor in cell extracts, but they are deficient in replication protein A (RPA) function. Extracts from cells treated with high levels of C-1027 (10 nM) do show the presence of a trans-acting inhibitor of DNA replication. The deficiency in RPA in extracts from cells treated with low levels of C-1027 can be fully complemented by the addition of exogenous RPA, and may be due to a C-1027-induced decrease in the extractability of RPA. This decrease in the extractability of RPA correlates with the appearance of many extraction-resistant intranuclear RPA foci. The trans-acting inhibitor of DNA replication induced by treatment of cells with high levels of C-1027 (10 nM) is DNA-dependent protein kinase (DNA-PK). DNA-PK is activated by the presence of DNA fragments induced by C-1027 treatment, and can be abrogated by removal of the DNA fragments. Although it is activated by DNA damage and phosphorylates RPA, DNA-PK is not required for either RPA focalization or loss of RPA replication activity.
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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/Aminoglycosides,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/C 1027,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enediynes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RPA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Replication Protein A
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14661-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11724580-Aminoglycosides,
pubmed-meshheading:11724580-Anti-Bacterial Agents,
pubmed-meshheading:11724580-Cell Line, Transformed,
pubmed-meshheading:11724580-Cell Nucleus,
pubmed-meshheading:11724580-DNA,
pubmed-meshheading:11724580-DNA, Viral,
pubmed-meshheading:11724580-DNA Damage,
pubmed-meshheading:11724580-DNA Replication,
pubmed-meshheading:11724580-DNA-Activated Protein Kinase,
pubmed-meshheading:11724580-DNA-Binding Proteins,
pubmed-meshheading:11724580-Enediynes,
pubmed-meshheading:11724580-Enzyme Activation,
pubmed-meshheading:11724580-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:11724580-HeLa Cells,
pubmed-meshheading:11724580-Humans,
pubmed-meshheading:11724580-Intracellular Fluid,
pubmed-meshheading:11724580-Nuclear Proteins,
pubmed-meshheading:11724580-Phosphorylation,
pubmed-meshheading:11724580-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11724580-Replication Protein A
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pubmed:year |
2001
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pubmed:articleTitle |
DNA damage by the enediyne C-1027 results in the inhibition of DNA replication by loss of replication protein A function and activation of DNA-dependent protein kinase.
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pubmed:affiliation |
Department of Microbiology & Biochemistry, State University of New York at Buffalo, School of Medicine & Biomedical Sciences, Buffalo, New York 14214, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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