- The G1 phase begins with the generation of daughter cells following cytokinesis and ends when daughter cells are ready to replicate their genomic DNA.
- G1 is the longest phase of the cell cycle in most mammalian cell types where the decision to divide or not to divide is made.
- If a cell decides to divide, it progresses to the S phase; otherwise, it enters a resting phase called the G0 phase.
- Most of our body cells as well as cells in culture have G1 DNA content. This is clearly reflected in flow cytometry analysis of propidium iodide stained cells.
- Most normal cells require growth factors/mitogens and attachment to the extracellular matrix (ECM) in order to proceed through the G1 phase and enter the S phase (replication of genome). These signaling pathways lead to the synthesis of D-type cyclins which bind with CDK4/6 and drive the progression of the G1 phase.
- Cells need growth factors/mitogens to pass through the restriction point. Once a cell passes through the restriction point, cell cycle progression is no longer dependent on growth factors/mitogens.
- The transition from the G1 phase to S phase requires activation of E2F transcription factors which are essential for S phase gene transcription.
- Normally E2F is present in the cell as an inactive form in a complex with Retinoblastoma (Rb) proteins. This complex is broken when Rb is hyperphosphorylated by CDKs.
- Initial phosphorylation of Rb is achieved by CDK4/6-Cyclin D complex and later by CDK2-Cyclin E complex.
- Activation of CDKs is a complex process and is controlled at multiple levels (phosphorylation/dephosphorylation, association with regulatory partners cyclins).
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