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Updated: Jun 8, 2026
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Cyclin-dependent kinase 9-cyclin K functions in the replication stress response
David S Yu1, Runxiang Zhao, Emory L Hsu
1Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
EMBO Reports
|October 9, 2010
Summary
Cyclin-dependent kinase 9 (CDK9) complexed with cyclin K, not cyclin T, acts in DNA replication stress response. This CDK9-cyclin K complex maintains genome integrity by limiting DNA damage during replication stress.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cyclin-dependent kinase 9 (CDK9) typically functions with cyclin T in transcription elongation.
- The role of CDK9 when complexed with cyclin K is less understood.
- Replication stress poses a significant threat to genome stability.
Purpose of the Study:
- To investigate the function of CDK9 in the context of replication stress.
- To determine the specific cyclin partners of CDK9 involved in DNA damage response.
- To elucidate the role of CDK9-cyclin K complexes in maintaining genome integrity.
Main Methods:
- Synthetic lethal RNA interference screening in human cells.
- Analysis of DNA damage signaling and replication recovery.
- Chromatin immunoprecipitation to assess protein localization.
- Co-immunoprecipitation to study protein interactions.
Main Results:
- Loss of CDK9 activity increases spontaneous DNA damage signaling during replication.
- CDK9-cyclin K complexes, not CDK9-cyclin T, are responsible for this effect.
- CDK9 accumulates on chromatin under replication stress and limits single-stranded DNA.
- CDK9 and cyclin K interact with ATR and other checkpoint proteins.
Conclusions:
- CDK9-cyclin K complexes play a direct role in checkpoint pathways responding to replication stress.
- This complex is crucial for maintaining genome integrity under conditions of DNA damage.
- CDK9-cyclin K represents a novel target for understanding and potentially treating diseases associated with genomic instability.
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In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
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