Related Concept Videos
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
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
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.
Yongxin Zou1, Jun Mi, Wenxing Wang
1Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
The Journal of Cell Biology
|March 13, 2013
Summary
CUL4B regulates DNA replication licensing by controlling CDC6 stability via CDK2. This pathway involves CUL4B repressing miR-372/373, which target CDK2, ensuring proper cell cycle progression.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- Cullin-RING ubiquitin ligases (CRLs) are crucial for cell cycle regulation.
- Mutations in X-linked CUL4B cause developmental disorders, and CUL4B deficiency is detrimental in vivo.
- CUL4B's role in DNA replication licensing remained largely unexplored.
Purpose of the Study:
- To elucidate the function of CUL4B in DNA replication licensing.
- To identify the molecular mechanisms by which CUL4B influences replication.
- To establish the relationship between CUL4B, CDK2, and CDC6 in cell cycle control.
Main Methods:
- Investigated CUL4B's role in replication licensing using cellular models.
- Analyzed the interaction and regulation between CUL4B, CDK2, CDC6, and MCM2.
- Examined the effect of CUL4B on microRNA expression (miR-372/373) and their targets (CDK2).
Main Results:
- CUL4B positively regulates the licensing factor CDC6, promoting MCM2 loading onto chromatin.
- CDK2 mediates CUL4B's positive regulation of CDC6 by protecting it from APC(CDH1)-mediated degradation.
- CUL4B up-regulates CDK2 by repressing miR-372 and miR-373, which target CDK2.
Conclusions:
- A novel CUL4B-CDK2-CDC6 signaling cascade regulates DNA replication licensing.
- This pathway is essential for pre-replication complex assembly during the G1 phase.
- CUL4B plays a critical role in ensuring proper cell cycle progression and DNA replication.