re-entry into mitotic cell cycle

Definition

Target type: biologicalprocess

The resumption of the mitotic cell division cycle by cells that were in a quiescent or other non-dividing state. [GOC:krc]

Re-entry into the mitotic cell cycle is a tightly regulated process that ensures proper cell division and prevents uncontrolled proliferation. This process is triggered by various internal and external signals, including growth factors, nutrients, and DNA damage response. The following steps outline the key events involved in re-entry into the mitotic cell cycle:

1. **G1 Phase Transition:** The first step involves transitioning from the G1 phase (first gap phase) of the cell cycle, where cells grow and synthesize proteins, into the S phase (synthesis phase), where DNA replication occurs. This transition is controlled by the restriction point (R point), a crucial checkpoint that ensures adequate cell size, sufficient nutrients, and proper DNA integrity before committing to DNA replication.

2. **Cyclin-Dependent Kinase (CDK) Activation:** The key regulators of the cell cycle are CDKs, a family of protein kinases that are activated by binding to cyclins. Specifically, cyclin D and E bind to CDK4 and CDK6, respectively, leading to their activation. These complexes phosphorylate the retinoblastoma protein (Rb), which is a tumor suppressor protein that normally inhibits cell cycle progression.

3. **Rb Phosphorylation and E2F Activation:** Phosphorylation of Rb by CDK4/6-cyclin complexes leads to its inactivation and the release of the transcription factor E2F. E2F plays a critical role in promoting gene expression required for S phase entry, including DNA replication genes and cyclin A expression.

4. **S Phase Entry:** The activation of E2F triggers the expression of genes necessary for DNA replication, leading to the initiation of S phase. During S phase, DNA replication occurs with high fidelity, ensuring that each daughter cell receives a complete and accurate copy of the genome.

5. **G2 Phase Transition:** After S phase, cells enter the G2 phase (second gap phase), where they further grow and prepare for mitosis. During G2, the cell continues to synthesize proteins and organelles necessary for cell division. The G2 checkpoint ensures that DNA replication is complete and any damage is repaired before proceeding to mitosis.

6. **Mitosis and Cell Division:** Finally, the cell enters the mitotic (M) phase, characterized by chromosome condensation, spindle formation, and sister chromatid separation. Cyclin B binds to CDK1 (also known as MPF, mitosis promoting factor), which triggers the activation of mitotic kinases, leading to the phosphorylation of numerous proteins involved in mitotic events.

7. **Exit from the Cycle:** After successful mitosis, daughter cells can enter either a new G1 phase, restarting the cycle, or enter a quiescent state known as G0, where they are not actively dividing.

Overall, re-entry into the mitotic cell cycle is a complex and precisely regulated process that ensures proper cell division and genome integrity. This process is essential for development, growth, and repair of tissues. However, dysregulation of these processes can contribute to uncontrolled cell proliferation and cancer development.'"

Proteins (1)

Compounds (70)