Cell & Developmental Biology
Open Access

Cyclin-Dependent Kinases as Control Systems in Cell Cycle

Long Ke Jon^{* *}Correspondence: Long Ke Jon, Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center (QBiC), Osaka, Japan, Email:

Author info »

Description

The cell cycle is a highly regulated and precisely organized series of events that occur in eukaryotic cells, leading to cell growth, replication, and division. It is important for maintaining tissue integrity, enabling growth and development, and repairing damaged tissues. This complex process ensures the precise and reliable transfer of genetic information without significant errors or alterations from one generation of cells to the next. For instance, in a developing embryo, the cell cycle is responsible for the rapid cell divisions that occur to form the various tissues and organs of the organism. This process starts with a single fertilized egg cell and leads to the formation of billions of specialized cells that make up the entire organism. Any disruption in this regulation can lead to developmental abnormalities and birth defects.

Cell cycle phases

G1 Phase (Gap 1): The cell exits the previous M phase and enters G1. During G1, the cell grows, increases its organelles, and prepares for DNA replication. The G1 phase also serves as a checkpoint to ensure that conditions are favorable for cell division.

S Phase (Synthesis): DNA replication occurs in this phase. Each chromosome is duplicated, resulting in two sister chromatids connected by a centromere. At the end of the S phase, the cell has twice the DNA content it had in G1.

G2 Phase (Gap 2): Further growth and preparation for cell division. The cell checks its DNA for errors and initiates repairs if necessary. The G2 phase also acts as a checkpoint to ensure that DNA is intact and ready for mitosis.

Prophase: Chromosomes condense and become visible as distinct structures. The nuclear envelope begins to break down.

Metaphase: Chromosomes align at the cell's equatorial plane, known as the metaphase plate. Each sister chromatid is attached to a spindle fiber.

Anaphase: Sister chromatids are separated and pulled toward opposite poles of the cell. Each chromatid is considered an independent chromosome once separated.

Telophase: Chromatids reach the cell poles. The nuclear envelope re-forms around each set of chromosomes, resulting in two distinct nuclei.

Cytokinesis: Cytokinesis is the process that divides the rest of the cell, including the cytoplasm and organelles, into two daughter cells. In animal cells, this often involves the formation of a contractile ring that pinches the cell membrane, resulting in two separate daughter cells. The completion of cytokinesis results in two genetically identical daughter cells, each with a full complement of organelles and the same genetic information as the parent cell. These daughter cells can then enter G1 of the cell cycle to continue growing and prepare for future divisions.

Regulator of the cell cycle

Cyclin-Dependent Kinases (CDKs) are a family of essential enzymes that play a central role in regulating the progression of the cell cycle. These protein kinases are named for their dependency on cyclin proteins, which bind to and activate them at specific points in the cell cycle, thus controlling cell cycle transitions and ensuring orderly progression. CDKs are inactive in their unbound form and require association with specific cyclin proteins to become active. The resulting cyclin-CDK complexes drive the cell cycle by phosphorylating target proteins. Checkpoints are control mechanisms that monitor the integrity of DNA and other factors before allowing the cell cycle to proceed.

Different CDK-cyclin complexes are active at various stages of the cell cycle. For example, the G1/S checkpoint is controlled by the cyclin D-CDK4/6 complex, and the G2/M checkpoint is regulated by the cyclin B-CDK1 complex. CDKs phosphorylate specific target proteins, including Retinoblastoma Protein (Rb) and the Anaphase-Promoting Complex/Cyclosome (APC/C). These phosphorylation events trigger cell cycle transitions and control the degradation of certain proteins. Dysregulation of CDK activity is associated with cancer. CDK inhibitors, such as palbociclib and abemaciclib, are used in cancer therapy to inhibit excessive CDK activity, preventing uncontrolled cell division.

Conclusion

Understanding the cell cycle is fundamental to fields such as cancer research, developmental biology, and regenerative medicine. Dysregulation of the cell cycle can lead to uncontrolled cell growth and is a hallmark of cancer. The study of CDKs is important to understanding the cell cycle, cancer biology, and the development of targeted cancer therapies. CDKs serve as key players in the complex network of cell cycle regulation, making them critical subjects of research in both basic and clinical biology.