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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2010-10-27
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pubmed:abstractText |
Cyclin-dependent kinase 9 (CDK9) is a well-characterized subunit of the positive transcription elongation factor b complex in which it regulates transcription elongation in cooperation with cyclin T. However, CDK9 also forms a complex with cyclin K, the function of which is less clear. Using a synthetic lethal RNA interference screen in human cells, we identified CDK9 as a component of the replication stress response. Loss of CDK9 activity causes an increase in spontaneous levels of DNA damage signalling in replicating cells and a decreased ability to recover from a transient replication arrest. This activity is restricted to CDK9-cyclin K complexes and is independent of CDK9-cyclin T complex. CDK9 accumulates on chromatin in response to replication stress and limits the amount of single-stranded DNA in cells under stress. Furthermore, we show that CDK9 and cyclin K interact with ataxia telangiectasia and Rad3-related protein and other checkpoint signalling proteins. These results reveal an unexpectedly direct role for CDK9-cyclin K in checkpoint pathways that maintain genome integrity in response to replication stress.
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pubmed:grant |
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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 |
Nov
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pubmed:issn |
1469-3178
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
876-82
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pubmed:dateRevised |
2011-11-1
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pubmed:meshHeading |
pubmed-meshheading:20930849-Cell Cycle,
pubmed-meshheading:20930849-Cell Line, Tumor,
pubmed-meshheading:20930849-Chromatin,
pubmed-meshheading:20930849-Cyclin-Dependent Kinase 9,
pubmed-meshheading:20930849-Cyclins,
pubmed-meshheading:20930849-DNA,
pubmed-meshheading:20930849-DNA Replication,
pubmed-meshheading:20930849-Gene Silencing,
pubmed-meshheading:20930849-Humans,
pubmed-meshheading:20930849-Hydroxyurea,
pubmed-meshheading:20930849-Protein Binding,
pubmed-meshheading:20930849-Replication Protein A,
pubmed-meshheading:20930849-Stress, Physiological
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pubmed:year |
2010
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pubmed:articleTitle |
Cyclin-dependent kinase 9-cyclin K functions in the replication stress response.
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pubmed:affiliation |
Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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