2.3 Cell cycle and division

Cell division is the foundation of life, growth, and reproduction. The cell cycle orchestrates this process, guiding cells through stages of growth, DNA replication, and division. Understanding these mechanisms is crucial for grasping how organisms develop and maintain themselves.

Mitosis and meiosis are two types of cell division with distinct purposes. Mitosis produces identical daughter cells for growth and repair, while meiosis creates diverse gametes for sexual reproduction. Both processes are tightly regulated to ensure genetic stability and prevent errors that could lead to diseases like cancer.

Cell cycle stages and characteristics

Interphase and its subdivisions

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• The cell cycle consists of interphase and the mitotic phase (M phase)
• Interphase is subdivided into G1, S, and G2 phases
• During G1 phase, the cell grows in size, synthesizes proteins, and prepares for DNA replication
  • The duration of G1 varies among cell types and can be influenced by external factors (nutrient availability, growth factors)
• S phase is characterized by DNA replication, resulting in the doubling of the cell's genetic material
  • Each chromosome now consists of two sister chromatids
• In G2 phase, the cell continues to grow and synthesize proteins in preparation for cell division
  • Organelles are duplicated (centrosomes, mitochondria)
  • The cell ensures that DNA replication has been completed accurately

M phase and quiescent state

• M phase is composed of mitosis (nuclear division) and cytokinesis (cytoplasmic division)
  • Mitosis is further divided into prophase, metaphase, anaphase, and telophase
• Some cells exit the cell cycle and enter a quiescent state called G0, where they remain metabolically active but do not divide
  • Cells in G0 can re-enter the cell cycle under appropriate conditions (tissue damage, hormonal stimulation)
• The duration of the cell cycle varies among different cell types
  • Rapidly dividing cells (embryonic cells, adult stem cells) have shorter cell cycles
  • Slowly dividing or non-dividing cells (neurons, muscle cells) have longer cell cycles or remain in G0

Checkpoints in cell cycle regulation

Types of cell cycle checkpoints

• Cell cycle checkpoints are control mechanisms that ensure the proper progression of the cell through the cycle
  • Maintain genomic integrity and prevent uncontrolled cell division
• The G1 checkpoint, also known as the restriction point in mammalian cells, checks for cell size, nutrient availability, and growth factors before committing to DNA replication
• The G1/S checkpoint ensures that the cell is ready for DNA replication and that the DNA is not damaged before proceeding to S phase
• The intra-S checkpoint monitors the progress of DNA replication and arrests the cell cycle if DNA damage is detected, allowing time for repair
• The G2/M checkpoint assesses cell size and ensures that DNA replication is complete and error-free before the cell enters mitosis
• The spindle assembly checkpoint (SAC) in metaphase ensures proper attachment of spindle fibers to kinetochores and equal distribution of chromosomes before proceeding to anaphase

Molecular regulators of checkpoints

• Checkpoint regulation involves various proteins, such as cyclins, cyclin-dependent kinases (CDKs), and tumor suppressor proteins
  • Cyclins and CDKs form complexes that drive the cell cycle progression
  • Tumor suppressor proteins (p53, RB) act as negative regulators of the cell cycle
• Dysregulation of cell cycle checkpoints can lead to uncontrolled cell division and contribute to the development of cancer
  • Mutations in tumor suppressor genes (p53, RB) can result in checkpoint failure and genomic instability
• DNA damage response pathways (ATM/ATR signaling) are activated at checkpoints to halt the cell cycle and initiate repair mechanisms
  • If the damage is irreparable, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of mutations

Process of mitosis and its importance

Stages of mitosis

• Mitosis is a process of nuclear division that results in the formation of two genetically identical daughter cells from a single parent cell
• During prophase, chromatin condenses into visible chromosomes, the nuclear envelope breaks down, and the mitotic spindle begins to form
  • Centrosomes, containing centrioles, migrate to opposite poles of the cell
• In metaphase, chromosomes align at the equatorial plane of the cell, with spindle fibers attached to the kinetochores of sister chromatids
  • The spindle assembly checkpoint (SAC) ensures proper attachment and tension of spindle fibers
• During anaphase, sister chromatids separate and are pulled towards opposite poles of the cell by the shortening of spindle fibers
  • Cohesion proteins, which hold sister chromatids together, are cleaved by separase
• In telophase, chromosomes decondense, the nuclear envelope re-forms around the separated chromosomes, and the spindle apparatus disassembles
  • Nucleoli reappear, marking the end of mitosis

Cytokinesis and the importance of mitosis

• Cytokinesis, the division of the cytoplasm, occurs concurrently with telophase
  • In animal cells, this involves the formation of a cleavage furrow, which pinches the cell membrane inward
  • In plant cells, a cell plate forms from vesicles derived from the Golgi apparatus and grows centripetally to divide the cytoplasm
• Mitosis is essential for growth, development, and tissue repair in multicellular organisms
  • Allows for the production of genetically identical cells to increase cell number and replace damaged or dead cells
• Mitosis also plays a role in asexual reproduction, where offspring arise from a single parent and are genetically identical to the parent
  • Examples include binary fission in prokaryotes and budding in some eukaryotes (hydra, yeast)

Mitosis vs meiosis

Key differences between mitosis and meiosis

• Mitosis produces two genetically identical daughter cells, while meiosis produces four genetically diverse haploid gametes or spores
• Mitosis involves one cell division, whereas meiosis involves two consecutive cell divisions (meiosis I and meiosis II)
  • Meiosis I is a reductional division, separating homologous chromosomes
  • Meiosis II is an equational division, separating sister chromatids
• In mitosis, chromosomes replicate once, while in meiosis, chromosomes replicate only once, followed by two rounds of segregation
• Mitosis maintains the diploid chromosome number, while meiosis reduces the chromosome number by half, resulting in haploid cells

Genetic variation and errors in cell division

• Crossing over and independent assortment during meiosis I contribute to genetic variation in the resulting gametes or spores
  • Crossing over involves the exchange of genetic material between homologous chromosomes
  • Independent assortment of chromosomes leads to random combinations of maternal and paternal chromosomes
• Mitosis occurs in somatic cells for growth and repair, while meiosis occurs in germ cells or reproductive structures to produce gametes or spores for sexual reproduction
  • Gametes (sperm, egg) fuse during fertilization to restore the diploid chromosome number in the zygote
• Errors in mitosis can lead to somatic mutations and contribute to cancer development
  • Aneuploidy (abnormal chromosome number) and chromosomal instability are hallmarks of many cancers
• Errors in meiosis can result in chromosomal abnormalities and genetic disorders in offspring
  • Nondisjunction (failure of chromosomes to separate) can lead to trisomy (Down syndrome) or monosomy (Turner syndrome)