Cell Cycle Checkpoint - G₁ (Restriction) Checkpoint

G₁ (Restriction) Checkpoint

The first checkpoint is located at the end of the cell cycle's G₁ phase, just before entry into S phase, making the key decision of whether the cell should divide, delay division, or enter a resting stage. Many cells stop at this stage and enter a resting state called G₀. Liver cells, for instance, enter mitosis only around twice a year. The G₁ checkpoint is where eukaryotes typically arrest the cell cycle if environmental conditions make cell division impossible or if the cell passes into G₀ for an extended period. In animal cells, the G₁ phase checkpoint is called the restriction point, and in yeast cells it is called the Start point. The restriction point is controlled mainly by action of the CKI- p16 (CDK inhibitor p16). This protein inhibits the CDK4/6 and ensures that it can no longer interact with cyclin D1 to cause the cell cycle progression. In growth-induced or oncogenic-induced cyclin D expression, this checkpoint is overcome because the increased expression of cyclin D allows its interaction with CDK4/6 by competing for binding. Once active CDK4/6-CYCLIN D complexes form, they phosphorylate the tumor suppressor retinoblastoma (Rb), which relieves the inhibition of the transcription factor E2F. E2F is then able to cause expression of cyclin E, which then interacts with CDK2 to allow for G1-S phase transition. This brings the cell to the end of the first checkpoint, signaling the G0-G1-S-phase transition.

In simpler terms, the CDK inhibitor p16 inhibits another CDK from binding to its cyclin (D). When growth is induced, the expression of this cyclin is so high that they do bind. The new CDK/cyclin complex now phosphorylates retinoblastoma (a tumor suppressor). Un-phosphorylated retinoblastoma inhibits a transcription factor. This factor then brings about the G1-S phase transition.