The cell cycle is divided into four main stages: G1, S, G2, and M. The G2 phase, or “second gap,” occurs after the cell duplicates its genetic material in the S phase and immediately before division in the M (mitosis) phase. It functions as a critical bridge, ensuring the cell is fully prepared physically and genetically to create two healthy daughter cells.
Cellular Growth and Spindle Component Synthesis
The G2 phase is characterized by robust growth and intense biochemical activity. The cell significantly increases its overall volume and replenishes energy reserves depleted during S phase DNA replication. This ensures that the eventual daughter cells will have sufficient resources.
A major focus is the production of proteins needed for mitotic division. These include large quantities of microtubule proteins, such as tubulin, which are the building blocks of the mitotic spindle. This spindle apparatus separates the duplicated chromosomes during mitosis.
The cell also prepares its internal structures for partitioning between the two daughter cells. Organelles like the mitochondria and the Golgi apparatus are often duplicated or prepared during G2.
DNA Integrity and Replication Checkpoint
The G2 phase acts as the final quality control check, known as the G2/M checkpoint, before division. This surveillance mechanism halts progression into mitosis if any issues are detected. The cell checks for two conditions: whether DNA replication was completed during the S phase and whether any DNA damage is present.
If the checkpoint detects incomplete replication or lesions in the DNA, it triggers a pause in the cell cycle. This pause allows DNA repair mechanisms to correct the errors, preventing the transmission of mutations to daughter cells. Specific sensor proteins, such as the kinases ATM and ATR, detect the damage and activate signaling pathways to arrest the cell in G2.
If the DNA damage is too extensive or irreparable, the cell may initiate programmed cell death, known as apoptosis. This action serves to protect the organism by preventing the proliferation of a compromised cell. Only when all checks are cleared and repair is successful is the cell permitted to proceed toward mitosis.
Mechanisms for Initiating Mitosis
The transition from G2 into the M phase is controlled by a molecular switch involving specific regulatory proteins. The core components are Cyclin-Dependent Kinases (CDKs) and their activating partners, cyclins. Completion of preparatory steps and clearance of the G2 checkpoint leads to the accumulation and activation of the Mitosis Promoting Factor (MPF).
MPF is a complex formed by Cyclin B binding to the CDK enzyme, typically CDK1. Throughout G2, Cyclin B levels gradually increase, but the MPF complex remains inactive due to inhibitory phosphorylation, often maintained by enzymes like Wee1 and Myt1. Activation is triggered by the phosphatase enzyme Cdc25, which removes these inhibitory phosphate groups.
Once fully activated, MPF phosphorylates target proteins that initiate the physical events of prophase. This includes the phosphorylation of nuclear lamins, causing the breakdown of the nuclear envelope, and the phosphorylation of histone proteins, promoting the condensation of duplicated DNA into visible chromosomes.