The cell cycle represents a fundamental process for all living organisms, orchestrating growth, repair, and reproduction. This intricate series of events is broadly categorized into two main phases: interphase and the mitotic (M) phase. Interphase, the period during which a cell grows and copies its DNA, consists of three sub-phases: G1, S, and G2. The G2 phase serves as the final preparatory stage, preceding the cell’s entry into cell division.
G2 Phase: The Final Preparations
The G2 phase is characterized by a period of cellular activity, as the cell undergoes its final preparations for division. During this stage, the cell continues to grow and actively replenishes its energy reserves, ensuring it has sufficient resources for the energetic demands of mitosis. This phase involves synthesis of proteins and various organelles crucial for cell division.
A key activity in G2 is the production of proteins like tubulin, which are the building blocks for microtubules. These microtubules are essential for forming the mitotic spindle, a structure that will accurately separate chromosomes during cell division. Histones, proteins vital for compacting and organizing DNA into chromosomes, are also synthesized during this time. Additionally, the duplication and maturation of centrosomes, which began in the S phase, are completed in G2, preparing them to organize the mitotic spindle poles.
The G2 Checkpoint: Ensuring Readiness
A critical regulatory point in the cell cycle, known as the G2 checkpoint or G2/M checkpoint, operates within the G2 phase. This checkpoint acts as a crucial control mechanism, evaluating the cell’s internal state and external environment before allowing it to commit to mitosis. Its primary function is to maintain genomic stability by preventing cells with damaged or incompletely replicated DNA from proceeding to division.
The G2 checkpoint rigorously verifies two primary conditions: the complete and accurate replication of the cell’s DNA, which occurred during the preceding S phase, and the absence of any DNA damage. If issues such as unreplicated DNA or DNA lesions are detected, the cell cycle is halted at this point. This pause provides an opportunity for DNA repair mechanisms to correct any errors, thereby preventing the propagation of genetic abnormalities to daughter cells.
Molecular players are activated in response to DNA damage, inhibiting progression into mitosis. Tumor suppressor protein p53 also plays a role by activating cell cycle arrest or, if the damage is irreparable, triggering programmed cell death. This ensures that only healthy, prepared cells enter mitosis, safeguarding genetic integrity.
The Transition to Mitosis
The cell’s progression from the G2 phase into the mitotic phase is governed by a molecular switch, regulated by a protein complex called Mitosis-Promoting Factor (MPF). MPF is composed of two subunits: cyclin B, a regulatory protein, and cyclin-dependent kinase 1 (Cdk1). The accumulation and activation of MPF are the main events that trigger the onset of mitosis.
MPF’s activation involves phosphorylation and dephosphorylation of Cdk1. Inhibitory kinases keep Cdk1 inactive, while an activating phosphatase removes these inhibitory phosphates, activating Cdk1. Once a threshold of active MPF is reached, a feedback loop increases MPF activity.
The activated MPF then initiates several events characteristic of early mitosis by phosphorylating target proteins. It triggers the breakdown of the nuclear envelope. MPF also promotes the condensation of chromosomes. Furthermore, it contributes to the assembly of the mitotic spindle, the machinery responsible for chromosome separation. Once MPF is sufficiently active, the transition into mitosis becomes irreversible, committing the cell to division.