The cell cycle is the ordered sequence of events that results in a cell dividing into two daughter cells. This cycle is broadly divided into two major parts: interphase, where the cell grows and copies its DNA, and the mitotic (M) phase, where the cell physically divides. Interphase itself consists of three sub-phases: G1, S, and G2.
The G2 phase, or “Gap 2,” is the final preparatory stage occurring after DNA replication in the S phase and immediately before mitosis. Its primary function is to act as a quality control gate, ensuring the cell is ready for division. During G2, the cell confirms the integrity of its newly copied genetic material and accumulates necessary structural components for successful separation.
Physical Preparation and Resource Accumulation
During the G2 phase, the cell undergoes rapid growth to increase its total volume and cellular mass. This final expansion ensures that the resulting daughter cells will be of adequate size to function properly after division. The cell also replenishes its energy reserves, storing adenosine triphosphate (ATP) to power chromosome movement and cell separation during mitosis.
Protein synthesis occurs, creating the specialized molecules needed for the upcoming M phase. One important structural protein synthesized is tubulin, the building block of microtubules that will form the mitotic spindle apparatus. Other proteins, such as condensin, are also produced, which are necessary to compact the long strands of duplicated DNA into visible chromosomes.
Organelle duplication is a continuous process throughout interphase, but it is completed in G2 to ensure equitable distribution to the two new cells. Organelles like mitochondria and peroxisomes must complete their replication to maintain the energy and metabolic capacity of the daughter cells. The cell also begins to reorganize its internal structure, including the dissolution of the existing cytoskeleton, freeing up components that will be repurposed for the mitotic spindle.
The G2 DNA Damage Checkpoint
The G2/M DNA damage checkpoint acts as the cell’s final quality assurance gate. The cell cannot proceed into mitosis until this checkpoint confirms two things: that DNA replication in the S phase is fully complete and that the genome is free of errors. This mechanism protects the organism from inheriting genetic instability, which is a hallmark of many diseases.
Specialized sensor proteins, such as ATM and ATR, constantly monitor the DNA throughout the G2 phase. If these sensors detect breaks or incompletely replicated regions, they initiate a complex signaling cascade within the cell. This cascade involves activating a series of signaling molecules that relay the “stop” signal to the cell cycle machinery.
The “stop” signal ultimately works by inactivating the molecular trigger for mitosis, effectively arresting the cell in G2. This pause provides the cell with time to activate various DNA repair pathways, like homologous recombination, which uses the intact sister chromatid as a template to fix the damaged strand. Cell cycle arrest is maintained until the integrity of the DNA is restored and the checkpoint is satisfied.
If the DNA damage is too extensive or irreparable, the cell cannot risk passing on a flawed genome. In this scenario, the G2 checkpoint can initiate the process of apoptosis, or programmed cell death. Apoptosis removes the severely damaged cell from the population, preventing its proliferation and maintaining the health and stability of the tissue.
Final Triggers for Mitotic Entry
Once the cell has completed its growth, accumulated resources, and passed the G2 DNA damage checkpoint, it must receive the molecular “go” signal to commit to division. This signal comes from the activation of a complex known as the Maturation-Promoting Factor (MPF). MPF is a heterodimer composed of a regulatory protein, M-cyclin (specifically Cyclin B), and an enzyme, Cyclin-Dependent Kinase 1 (CDK1).
M-cyclin levels gradually accumulate throughout the G2 phase, binding to and forming a complex with CDK1. However, this complex remains inactive due to inhibitory phosphate groups added to the CDK1 subunit by other regulating enzymes. This regulation ensures the cell has built up the necessary components while remaining on hold until the checkpoint is cleared.
The final switch that triggers entry into mitosis is the sudden removal of these inhibitory phosphates by an activating enzyme called Cdc25 phosphatase. Once the inhibitory phosphate groups are stripped away, the MPF complex becomes fully active. This activation often occurs in a rapid, self-amplifying positive feedback loop, ensuring a swift and irreversible commitment to cell division.
The now-active MPF complex then begins to phosphorylate hundreds of target proteins throughout the cell. These phosphorylation events act as molecular instructions that initiate the first events of mitosis, such as the condensation of the duplicated chromosomes and the breakdown of the nuclear envelope. This cascade of activity marks the end of the G2 phase and the beginning of prophase, the first stage of the M phase.