4.6 - Cell Cycle

The Cell Cycle is the series of events that take place in a cell leading to its growth, replication, and division into two daughter cells. It's essential for the continuation of life, as all organisms arise from the division of preexisting cells.

Stages of the Cell Cycle

1. Interphase:

   • General Features: Comprising about 90% of a cell's life, interphase is the period during which the cell is not actively dividing but preparing for the division process.

   • Subphases:

     • G1 Phase (First Gap): During this initial stage, cells experience growth by producing proteins and increasing in size. Cells also
       perform their specific functions depending on their type within the organism.

     • S Phase (Synthesis): The cell replicates its DNA, ensuring that each new cell will have an identical set of chromosomes. This phase is crucial for the genetic fidelity of the daughter cells.

     • G2 Phase (Second Gap): The final preparations for cell division are made, including the production of proteins necessary for cell division.

     • G0 Phase: Not a part of the active cell cycle, this phase is where cells reside when they are not destined to divide. Cells like neurons enter this phase permanently, where they remain metabolically active but do not proceed to division.

2. M Phase (Mitotic Phase):

   • Mitosis: This is the process by which the cell's nucleus divides, resulting in two identical nuclei. It includes several steps: prophase, metaphase, anaphase, and telophase.

   • Cytokinesis: Following mitosis, cytokinesis divides the cell's cytoplasm, forming two distinct daughter cells each containing a nucleus and cellular organelles.

Regulation and Control

• Highly Regulated Process: The cell cycle is controlled by various checkpoints and regulatory molecules that ensure the cell is ready to proceed to the next stage. These mechanisms help prevent errors such as DNA damage, which can lead to diseases like cancer.

• External Signals: Cells may also receive signals from other cells that influence their progression through the cell cycle, particularly whether to enter or remain in the G0 phase.

Importance of the Cell Cycle

• Homeostasis and Growth: By regulating cell growth and division, organisms can maintain homeostasis, repair tissues, and grow.

• Genetic Stability: Accurate DNA replication and distribution during the cell cycle are vital for genetic stability, ensuring that each new cell receives a complete and unchanged set of genetic instructions.

Mitosis

Mitosis is a critical cellular process in eukaryotic organisms that ensures the accurate and equal distribution of a cell’s genetic material—its genome—into two genetically identical daughter cells. This process is vital for growth, tissue repair, and asexual reproduction in somatic (non-reproductive) cells.

Stages of Mitosis

Prophase

• Chromosome Condensation: During prophase, the cell's chromatin (the complex of DNA and proteins) condenses into visible structures called chromosomes. This condensation is necessary to organize the DNA and ensure its safe handling during cell division.

• Formation of Sister Chromatids: Each chromosome is replicated before mitosis, resulting in two identical copies called sister chromatids, which are joined together at a region known as the centromere.

• Spindle Formation: The mitotic spindle, a structure made of microtubules, begins to form. These microtubules originate from structures called centrosomes, which start to move towards opposite ends of the cell to organize the spindle apparatus.

Prometaphase

• Breakdown of the Nuclear Envelope: As mitosis progresses from prophase to prometaphase, the nuclear envelope surrounding the nucleus breaks down into fragments. This disassembly is crucial for allowing the mitotic spindle fibers access to the chromosomes.

• Further Chromosome Condensation: During prometaphase, chromosomes condense even more intensely than in prophase. This higher level of condensation is necessary to facilitate their movement during mitosis.

• Formation of Kinetochores:

  • Structure and Function: Each sister chromatid develops a kinetochore, a specialized protein structure that assembles at the centromere—the region where sister chromatids are joined.

  • Spindle Fiber Attachment: The kinetochores serve as attachment points for microtubules of the mitotic spindle, which are essential for moving chromosomes during mitosis.

Metaphase

• Alignment at the Metaphase Plate:

  • Chromosome Organization: During metaphase, the chromosomes align at the metaphase plate, an imaginary plane equidistant between the spindle's two poles. This alignment is not a physical structure but a critical organizational arrangement for chromosome segregation.

  • Purpose of Alignment: This precise alignment ensures that each daughter cell will receive an identical set of chromosomes during cell division. The alignment is regulated by the kinetochores attached to the microtubules extending from opposite spindle poles.

• Centrosome Positioning:

  • Spindle Pole Formation: By metaphase, the centrosomes, which organize the mitotic spindle fibers, have migrated to opposite poles of the cell. This positioning is crucial for the proper tension and alignment of chromosomes.

• Kinetochore and Microtubule Interaction:

  • Attachment and Tension: Kinetochores attach to the microtubules emanating from the centrosomes. Proper attachment and the building tension help align the chromosomes precisely at the metaphase plate, preparing them for separation during the next phase of mitosis.

Anaphase

• Separation of Chromatids:

  • Trigger for Separation: Anaphase begins when the centromeres that hold sister chromatids together are cleaved. This separation is facilitated by the pulling forces of the mitotic spindle, generated by the kinetochores.

  • Role of Kinetochores: Kinetochores play a critical role in the movement of chromosomes by attaching to microtubules and moving along them, which helps pull the chromatids apart.

• Chromosome Movement:

  • Toward Opposite Poles: Once separated, the chromosomes (previously sister chromatids) move rapidly toward opposite poles of the cell. This movement is a result of the microtubules shortening, pulling the chromosomes away from the metaphase plate.

• Cell Elongation:

  • Mechanism of Elongation: As the chromosomes move toward the poles, the cell itself elongates. This elongation is primarily due to the polar microtubules, which push against each other, stretching the cell.

Telophase

• Reformation of Nuclei:

  • Nuclear Envelope and Nucleoli: In telophase, the mitotic spindle disassembles, and the nuclear envelope begins to reform around each set of chromosomes at the poles, signifying the end of nuclear division. The nucleolus, which disassembles during prophase, also reappears within each new nucleus.

• Chromosome Decondensation:

  • Transition to Chromatin: The chromosomes that were highly condensed during mitosis begin to decondense, gradually reverting to the less compact chromatin structure. This decondensation is crucial for resuming normal cellular functions, particularly gene transcription.

• Completion of Mitosis:

  • Final Steps: The reformation of the nuclear structures and the decondensation of chromatin mark the completion of mitosis. The cell is now ready to proceed to cytokinesis, where the cytoplasm divides and the cell officially splits into two distinct daughter cells.

  • Note: Cytokinesis is connected with Mitosis but is not part of Mitosis.

Cytokinesis

Cytokinesis is the process during which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It typically occurs at the end of the mitotic phase, following telophase, and is essential for completing cell division. While mitosis deals with the division of the nucleus, cytokinesis ensures that the cellular organelles and cytoplasm are evenly distributed between the two new cells.

Mechanism of Cytokinesis

• Formation of the Cleavage Furrow:

  • Initiation: In animal cells, cytokinesis is characterized by the formation of a cleavage furrow. This furrow is an indentation of the cell's membrane that begins to form during telophase.

  • Action: The furrow is created by a contractile ring composed of actin filaments and myosin motor proteins. As the ring contracts, it pulls the plasma membrane inward, gradually pinching the cell into two separate entities.

• Division of Cytoplasm and Organelles:

  • Equal Distribution: During cytokinesis, the cell's organelles—such as the endoplasmic reticulum, mitochondria, and Golgi apparatus—are distributed between the two forming daughter cells. This distribution is meticulously regulated to ensure that each daughter cell has the necessary machinery to survive and function independently.

  • Completion: The process is complete when the cleavage furrow contracts to the point that the cell is pinched in two, resulting in the formation of two separate and fully enclosed daughter cells, each with its own set of cellular components. 

Genome and Chromosomal Structures

• Genome Definition: The genome of a cell encompasses all of its genetic information, stored in the form of DNA.

• Prokaryotic DNA:

  • Structure: Typically consists of a single, circular chromosome.

  • Packaging: Lacks the complex chromosomal structure found in eukaryotes, with DNA often found freely floating within the cell.

• Eukaryotic DNA:

  • Structure: Comprises one or more linear chromosomes within the nucleus.

  • Packaging: DNA is wrapped around histone proteins, forming chromatin during interphase and condensing into chromosomes during mitosis.

DNA Organization in Eukaryotes

• Chromatin vs. Chromosomes:

  • Chromatin: Represents the loosely packed form of DNA which predominates during Interphase. This arrangement allows for easier access to DNA for replication and transcription.

  • Chromosomes: During Mitosis, DNA condenses into tightly packed structures known as chromosomes, facilitating their equal distribution to daughter cells.

Types of Eukaryotic Cells

• Somatic Cells:

  • Definition: These are the body cells that make up most of an organism.

  • Ploidy: Diploid (2n), containing two sets of chromosomes, one from each parent.

  • Division: Somatic cells divide by mitosis to facilitate growth, repair, and asexual reproduction.

• Gametes:

  • Definition: Reproductive cells, such as eggs and sperm.

  • Ploidy: Haploid (n), having a single set of chromosomes.

  • Division: Gametes are produced by meiosis, which reduces the chromosome number by half to ensure genetic diversity through sexual reproduction.

Special Considerations: Binary Fission in Prokaryotes

• Mechanism: Unlike eukaryotic cells, bacteria and some unicellular eukaryotes reproduce via binary fission, a simpler and generally less regulated process.

• Implications: The lack of complex regulation can lead to mutations, some of which may confer resistance to antibiotics, posing significant challenges in medical treatments.

Tracking Chromosomes Through the Stages of Mitosis in Human Cells

Basic Definitions

• Chromosome: A structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.

• Chromatid: Each of the two thread-like strands into which a chromosome divides longitudinally during cell division. Each contains a double helix of DNA.

Chromosome and Chromatid Counts During Mitosis

1. Initial Condition in a Parent Cell:

   • Diploid Number (2n = 46 in humans): This means the parent cell has 46 chromosomes, each made of a single chromatid before DNA replication.

2. After S Phase:

   • Chromosomes: Still counted as 46 because each chromosome, although consisting of two sister chromatids (after DNA replication), is considered one unit.

   • Chromatids: 92, because each of the 46 chromosomes has been replicated into a pair of sister chromatids.

3. Mitotic Stages:

   • Prophase:

     • Chromosomes: 46 (each still recognized as one unit comprising two sister chromatids).

     • Chromatids: 92.

   • Metaphase:

     • Chromosomes: 46 aligned at the metaphase plate.

     • Chromatids: 92, each pair of chromatids still connected at the centromere.

   • Anaphase:

     • Chromosomes: 92, as sister chromatids separate, each chromatid is now considered an individual chromosome.

     • Chromatids: 92, now separated and moving to opposite poles, counted as individual chromosomes.

   • Telophase:

     • Chromosomes: 92, as the separated chromatids reach the poles, begin to decondense.

     • Chromatids: 92, beginning to form two new nuclear envelopes.

4. Completion of Mitosis and Cytokinesis:

   • End of Mitosis (Cytokinesis completed):

     • Chromosomes: 46 in each daughter cell, as the cell returns to its original diploid state with each chromosome now having only one chromatid.

     • Chromatids: 46, each chromosome in the daughter cells now exists as a single chromatid.