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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2009-8-17
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pubmed:abstractText |
Cdk2 and cdk1 are individually dispensable for cell-cycle progression in cancer cell lines because they are able to compensate for one another. However, shRNA-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated S phase cell-cycle arrest and the phosphorylation of a subset of ATR/ATM targets after DNA damage. Loss of DNA damage-induced checkpoint control was caused by a reduction in formation of BRCA1-containing foci. Mutation of BRCA1 at S1497 and S1189/S1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of BRCA1-containing foci. Abrogation of checkpoint control after cdk1 depletion or inhibition in non-small-cell lung cancer cells sensitized them to DNA-damaging agents. Conversely, reduced cdk1 activity caused more potent G2/M arrest in nontransformed cells and antagonized the response to subsequent DNA damage. Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-10373534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-11046155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-11239454,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-11836499,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-17700700,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-17965729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-18171670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-8634697,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19683496-9267023
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-4164
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
327-39
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:19683496-BRCA1 Protein,
pubmed-meshheading:19683496-CDC2 Protein Kinase,
pubmed-meshheading:19683496-Cell Cycle Proteins,
pubmed-meshheading:19683496-Cell Line,
pubmed-meshheading:19683496-DNA Damage,
pubmed-meshheading:19683496-DNA Repair,
pubmed-meshheading:19683496-DNA-Binding Proteins,
pubmed-meshheading:19683496-Humans,
pubmed-meshheading:19683496-Mutation,
pubmed-meshheading:19683496-Phosphorylation,
pubmed-meshheading:19683496-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19683496-S Phase,
pubmed-meshheading:19683496-Signal Transduction,
pubmed-meshheading:19683496-Tumor Suppressor Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage.
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pubmed:affiliation |
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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