G1/S transition of mitotic cell cycle

Definition

Target type: biologicalprocess

The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated. [GOC:mtg_cell_cycle]

The G1/S transition, a critical checkpoint in the mitotic cell cycle, marks the commitment of a cell to replicate its DNA and divide. This transition is tightly regulated by a complex network of proteins, including cyclins, cyclin-dependent kinases (CDKs), and their inhibitors.

During G1 phase, the cell grows and accumulates necessary proteins and organelles. As the cell progresses through G1, it reaches a "restriction point" where it becomes committed to entering the S phase. The transition from G1 to S phase is driven by the activation of the cyclin-dependent kinase complex CDK2/cyclin E.

**Activation of CDK2/cyclin E:**

- **Cyclin E synthesis:** Expression of cyclin E is induced by growth factors and mitogens, promoting cell cycle progression.
- **CDK2 activation:** CDK2 is a kinase that requires phosphorylation on threonine 160 by CDK-activating kinase (CAK) for full activation.
- **Inhibitor removal:** The activity of CDK2/cyclin E is further regulated by inhibitors like p21 and p27. These inhibitors are degraded during G1, allowing CDK2 to become fully active.

**Role of CDK2/cyclin E in G1/S transition:**

- **Phosphorylation of target proteins:** Active CDK2/cyclin E phosphorylates a variety of proteins involved in DNA replication initiation, such as the origin recognition complex (ORC), DNA polymerase, and helicase.
- **Transcriptional regulation:** CDK2/cyclin E also regulates the expression of genes required for S phase progression, including those involved in DNA replication and repair.
- **Cell cycle progression:** The activity of CDK2/cyclin E drives the cell through the restriction point and into S phase, committing the cell to DNA replication and division.

**Regulation of G1/S transition:**

- **Growth factors and mitogens:** These signals stimulate cyclin E expression and promote CDK2 activation, promoting cell cycle progression.
- **DNA damage:** DNA damage activates checkpoint pathways that inhibit CDK2/cyclin E activity, preventing cell cycle progression until the damage is repaired.
- **Cellular stress:** Other stressors, such as nutrient deprivation or hypoxia, can also trigger cell cycle arrest at the G1/S checkpoint.

**Summary:**

The G1/S transition is a tightly regulated checkpoint that ensures proper cell cycle progression. It is driven by the activation of the CDK2/cyclin E complex, which phosphorylates key proteins involved in DNA replication and other S phase processes. This transition is regulated by a variety of factors, including growth signals, DNA damage, and cellular stress, ensuring that cells only progress through the cell cycle when conditions are favorable.'
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Proteins (37)

Compounds (580)