Cell Cycle

  • Cell cycle or cell division cycle refers to a series of coordinated events, that occur during cell proliferation.
  • Cell cycle regulation is a highly complex and conserved process in most eukaryotes.
  • Cell division is induced by external stimuli such as mitogens and growth factors while multilayered internal controls (e.g., cell cycle checkpoints) monitor the fidelity of cell cycle progression. When both requirements are met, precisely timed one-way transition of cell cycle phases proceeds and ultimately generates genetically identical daughter cells.
  • A typical cell cycle of mammalian cells is divided into four distinct phases:
  • G1, S, and G2 phases are collectively called interphase. The purpose of interphase is to synthesize all essential cellular components including duplication of the genome and make the cell ready for division.
  • G1 (Gap 1) phase: After cytokinesis, a mother cell generates two daughter cells. The G1 phase is the time between cytokinesis and S phase. This is the phase where cells take the decision ‘to divide’ or ‘not to divide’. If cells decide not to divide, a phase called ‘G0’ is established. If cells decide to divide, cells prepare for a new round of cell division which involves the synthesis of RNA and proteins, required for DNA synthesis. This results in an increase in cell size. G1, in most cells, is the longest phase of the cell cycle. Most dividing cells spend approximately 60% time in G1 phase. Furthermore, the progression of G1 phase is monitored by checkpoints (e.g., Restriction point, G1/S checkpoint).
  • S Phase: DNA replication occurs during the S (synthesis) phase. The intra-S-phase checkpoint monitors the progression through the S phase.
  • G2 (Gap 2) phase: New proteins are synthesized. Progression to the M phase from the G2 phase is monitored by the G2/M checkpoint.
  • M-phase: M-phase refers to the division of the nucleus (mitosis or karyokinesis) and cytoplasm (Cytokinesis). Mitosis involves nuclear membrane assembly/disassembly, chromosome condensation, mitotic spindle assembly, and segregation of sister chromatids. At the end of mitosis, cleavage furrow formation starts between the two daughter nuclei. The completion of the cleavage furrow and physical separation of the cell into two daughter cells occur during cytokinesis.
  • Periodic expression of specific cell cycle genes, called cyclins, forms an important regulatory control that ensures the smooth progression of the cell cycle. They together with their catalytic partners Cyclin-dependent kinases (CDKs) drive the progression of the cell cycle through different phases.
  • Cell cycle-dependent genes can be regulated at several levels:
    • Transcriptional (RNA synthesis rate)
    • Post-transcription (RNA stability and degradation)
    • Translation (Protein synthesis rate)
    • Post-translational level (protein modification e.g., phosphorylation and degradation)
  • A complete cell cycle event ultimately gives rise to two daughter cells from a mother cell. Specialized cell cycles, e.g., endoreduplication, asymmetrical cell division, cell division during development, and stem cell division, have also been reported.
  • Loss of control over the cell cycle can lead to uncontrolled cell proliferation and cancer.

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