The G1 phase is the first of four stages in the cell cycle, representing the initial part of a longer period called interphase. It follows cell division and precedes DNA replication. During this time, the cell is in a state of active growth, carries out its metabolic functions, and prepares for the subsequent stages. The duration of this phase can vary significantly, lasting from a few hours in rapidly dividing cells to much longer periods in other cell types.
Cellular Activities During G1 Phase
During the G1 phase, a cell undergoes substantial growth, increasing the volume of its cytoplasm and its overall size. This managed process ensures that when the cell divides, the two resulting daughter cells will be large enough to function correctly. As this phase is metabolically active, the cell dedicates significant energy to these growth processes.
A primary activity within the G1 phase is the synthesis of proteins and RNA. Messenger RNA (mRNA) molecules are transcribed from DNA, carrying instructions for building specific proteins. These proteins are required for cell maintenance and the upcoming demands of DNA replication. They have numerous functions, acting as enzymes for metabolic reactions and as structural components.
The cell also produces new organelles, the specialized structures within the cytoplasm that perform specific jobs. This includes forming additional mitochondria to meet high energy demands and creating more ribosomes for protein synthesis. Increasing the number of these structures prepares the cell for duplicating its genetic material and dividing.
This stage is also characterized by accumulating the molecular building blocks for the S phase. The cell stockpiles nucleotides, the individual units that make up DNA. This ensures a ready supply is available when DNA replication begins, allowing the process to proceed efficiently.
The G1 Checkpoint
A regulatory point exists late in the G1 phase known as the G1 checkpoint, or the restriction point in mammalian cells. This checkpoint serves as a decision-making hub where the cell assesses its internal state and external environment before committing to the cell cycle. The cell evaluates its size, the availability of nutrients, and the presence of signaling molecules called growth factors.
A primary assessment at this checkpoint is the integrity of the cell’s DNA. The cell scans its genetic material for damage, such as breaks or mutations, to ensure it does not replicate compromised DNA. If damage is detected, the cell cycle is halted to allow for repairs.
Progression through the G1 checkpoint is managed by proteins known as cyclins and cyclin-dependent kinases (CDKs), which act as accelerators of the cell cycle. When conditions are favorable, G1 cyclins accumulate and bind to their partner CDKs, activating them. This complex then phosphorylates other proteins that drive the cell into the S phase.
Conversely, tumor suppressor proteins function as the brakes. The retinoblastoma protein (pRb), in its active state, prevents the cell from progressing. When G1 cyclin-CDK complexes are active, they phosphorylate pRb, inactivating it and releasing the brakes. Another brake is the p53 protein, which becomes active in response to DNA damage and can halt the cell cycle to initiate DNA repair.
Outcomes of the G1 Phase
After the G1 checkpoint evaluations, a cell can proceed down one of several paths. The most common outcome for a healthy cell that meets all criteria is to advance into the S phase. Once past the restriction point, the cell is irreversibly committed to completing DNA replication, the G2 phase, and mitosis.
A cell that fails to meet the necessary conditions can exit the G1 phase and enter a quiescent, non-dividing state known as the G0 phase. In this state, the cell is metabolically active and performs its specialized functions but does not progress toward division. Some cells, like mature neurons, may remain in G0 permanently, while others, like liver cells, can re-enter the G1 phase in response to specific signals.
A third outcome is apoptosis, or programmed cell death. This pathway is triggered when the G1 checkpoint detects severe and irreparable DNA damage. Apoptosis is a regulated self-destruction mechanism that eliminates a cell with flawed genetic material, preventing the proliferation of damaged cells that could lead to disease.
G1 Phase and Cancer Development
Failures in the G1 phase’s regulatory mechanisms are frequent in cancer development. The G1 checkpoint is a barrier against uncontrolled cell proliferation. When the genes controlling this checkpoint are mutated, cells can lose the ability to regulate their division, a defining characteristic of cancer.
Mutations in genes that encode the “brake” proteins are common culprits. The TP53 gene, which produces the p53 protein, is one of the most frequently mutated genes in human cancers. A non-functional p53 protein cannot halt the cell cycle in response to DNA damage, allowing flawed cells to pass the G1 checkpoint and divide.
Similarly, mutations in the RB1 gene, which codes for the retinoblastoma protein (pRb), can disable another G1 safety mechanism. Without functional pRb to restrain the cell cycle, cells can advance into the S phase prematurely and without proper external growth signals. This failure of the G1 checkpoint leads to continuous cell division, driving tumor formation and growth.