Cell cycle, new cell life

The cell cycle is a tightly regulated process that controls cell division and growth, ensuring proper replication of genetic material and distribution to daughter cells. This fundamental process consists of four main phases: G1 (growth), S (DNA synthesis), G2 (preparation), and M (mitosis). Interphase, comprising G1, S, and G2 phases, is crucial for DNA replication and cell growth, while mitosis enables the physical division of the cell.

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Overview of the cell-cycle.

Phases of the cell cycle

The cell division consists of several distinct phases:

G1 Phase: Growth and Preparation

The G1 phase marks the cell’s initial growth stage, influenced by stress, environmental factors, and metabolic conditions. During this phase:

Cells synthesize essential proteins.
Organelles like ribosomes and mitochondria are amplified.
The cell grows in size, preparing for DNA replication.

S Phase: DNA Synthesis

In the S phase, DNA replication occurs, doubling the cell’s genetic material. Key events include:

Each chromosome replicates to form two identical sister chromatids.
The total DNA content is doubled, ensuring genetic material for two daughter cells.

G2 Phase: Preparation for Mitosis

After completing DNA replication, cells enter the G2 phase. In this stage:

Significant protein and lipid synthesis occurs.
DNA damage from replication, such as double-strand breaks, is repaired.
The cell undergoes rapid growth to prepare for mitosis.

M Phase: Mitosis and Cytokinesis

The M phase involves the division of the nucleus (mitosis) and cytoplasm (cytokinesis) to form two daughter cells. This phase includes:

Mitosis Sub-Stages: Prophase, prometaphase, metaphase, anaphase, and telophase.
Cytokinesis: Physical separation of cytoplasm to complete cell division.
Accurate chromosome and cytoplasmic segregation are critical for ensuring genetic stability.

G0 Phase: Resting Stage

After the M phase, cells may enter the G0 resting stage, where they temporarily or permanently cease division. This phase is common in differentiated or quiescent cells.

Components and cell cycle proteins

Cyclins

Cyclins are regulatory proteins that fluctuate in concentration throughout the cell division. They are categorized based on the phase they regulate:
- G1 Cyclins: Promote progression through the G1 phase.
- G1/S Cyclins: Facilitate the transition from G1 to S phase.
- S Cyclins: Activate processes necessary for DNA replication during the S phase.
- M Cyclins: Drive the events of mitosis (M phase) such as chromosome condensation and nuclear envelope breakdown

Cyclin-Dependent Kinases (CDKs)

CDKs are a family of enzymes that, when activated by binding to cyclins, phosphorylate specific target proteins to promote cell cycle progression. Each CDK is associated with a specific cyclin, forming a cyclin-CDK complex that is crucial for advancing through various checkpoints in the cell division.
CDKs remain at relatively constant levels throughout the cell division; however, their activity is tightly regulated by the availability of their corresponding cyclins.

Checkpoint Proteins

Checkpoints are critical control mechanisms that monitor the integrity of the cell division. Key proteins involved include:
- p53: A tumor suppressor protein that responds to DNA damage by halting the cell division and facilitating DNA repair or triggering apoptosis if damage is irreparable.
- Retinoblastoma Protein (Rb): Regulates the G1/S transition by binding to E2F transcription factors, inhibiting their activity until Rb is phosphorylated and inactivated.
- p21: An inhibitor of CDK activity that is activated by p53 in response to DNA damage, further enforcing cell cycle arrest.

Regulation of cell division

The interaction between cyclins and CDKs is essential for cell division progression. When a cyclin binds to its respective CDK, it induces a conformational change that activates the kinase, allowing it to phosphorylate target proteins involved in advancing the cell division stages.

The synthesis and degradation of cyclins are tightly regulated. Cyclins are produced at specific points in the cell cycle and degraded once their role is fulfilled, ensuring that CDKs are only active when needed. This regulation prevents premature progression through the cell cycle phases.
Additionally, external signals such as growth factors can stimulate cyclin synthesis, while internal signals like DNA damage can inhibit CDK activity, demonstrating how cells integrate various cues to maintain homeostasis during division.

What diseases are related to cell cycle ?

Defects in cell division regulation are a hallmark of many diseases, including:

Cancer: Uncontrolled cell division caused by mutations in key regulators.
Neurodegenerative Disorders: Aberrant cell division re-entry in neurons, contributing to diseases like Alzheimer’s.
Cardiovascular Diseases: Impaired cell division regulation in endothelial and smooth muscle cells affects vascular health.

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Cell cycle signaling pathway biomarker list

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Signaling Pathways

Signaling Pathways	Product ref	Informations
Cell Cycle	CC1H1	Download biomarker list

Species : Mus musculus (mouse)

Mouse Signaling Pathways

Signaling Pathways	Product ref	Informations
Cell Cycle	CC1M1	Download biomarker list

Species : Rattus norvegicus (rat)

Rat Signaling Pathways

Signaling Pathways	Product ref	Informations
Cell Cycle	*******	Biomarker list in progress.

Species : Sus Scrofa (Pig)

Pig Signaling Pathways

Signaling Pathways	Product ref	Informations
Cell Cycle	*******	Biomarker list in progress.

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Bibliography

1. Wang Z. Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling. Cells. (2021);10(12):3327.

2. Suski JM, et al. Targeting cell-cycle machinery in cancer. Cancer Cell. (2021);39(6):759-778.

3. Leal-Esteban LC, Fajas L. Cell cycle regulators in cancer cell metabolism. Biochim Biophys Acta Mol Basis Dis. (2020);1866(5):165715.

4. Łukasik P, et al. Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development–Review. Int J Mol Sci. (2021); 22(6): 2935.

5. García-Osta A, et al. p27, The Cell Cycle and Alzheimer´s Disease. Int J Mol Sci. (2022);23(3):1211.

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