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The Cell Cycle: Mechanisms and Regulation

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Chapter 12: The Cell Cycle

Introduction to the Cell Cycle

The cell cycle is the series of events that take place in a cell leading to its division and duplication. It is fundamental to the continuity of life, ensuring that genetic information is faithfully transmitted from one generation to the next. Cell division is essential for reproduction, growth, development, and tissue repair in living organisms.

  • Cell Division: The process by which a parent cell divides into two or more daughter cells.

  • Types of Cell Division:

    • Mitosis: Maintains chromosome number; daughter cells are genetically identical to the parent cell.

    • Meiosis: Reduces chromosome number by half; produces gametes (sperm and eggs), leading to genetic variation.

Mitosis vs Meiosis cartoon

Functions of Cell Division

Cell division serves different purposes in unicellular and multicellular organisms:

  • Unicellular Organisms: Cell division is a form of reproduction.

  • Multicellular Organisms:

    • Development from a fertilized cell

    • Growth

    • Repair of tissues

Examples of cell division: reproduction, growth, tissue renewal

Organization of Genetic Material

Genome and Chromosomes

The genome is the complete set of genetic material in a cell. In prokaryotes, the genome is typically a single DNA molecule, while in eukaryotes, it consists of multiple DNA molecules organized into chromosomes. Eukaryotic cells also contain mitochondrial DNA (mtDNA) and, in plants, chloroplast DNA (cpDNA).

  • Chromosomes: Structures that package and organize DNA with proteins (chromatin).

  • Somatic Cells: Non-reproductive cells with two sets of chromosomes (diploid).

  • Gametes: Reproductive cells with one set of chromosomes (haploid).

Stained chromosome

Chromosome Number and Ploidy

Each species has a characteristic number of chromosomes. The number of chromosome sets is referred to as ploidy:

  • Diploid (2n): Two sets of chromosomes (e.g., humans: 46 chromosomes).

  • Haploid (n): One set of chromosomes (e.g., human gametes: 23 chromosomes).

  • Polyploid: More than two sets of chromosomes, common in plants.

Abnormal chromosome numbers can lead to disorders such as Down Syndrome (trisomy 21).

Human karyotype with trisomy 21 (Down Syndrome)

Chromosome Structure and Replication

Before cell division, DNA is replicated, resulting in duplicated chromosomes composed of two sister chromatids joined at a region called the centromere. During division, sister chromatids separate, ensuring each daughter cell receives an identical set of chromosomes.

Chromosome structure with centromere and sister chromatids

The Cell Cycle Phases

Overview of the Cell Cycle

The cell cycle consists of interphase (about 90% of the cycle) and the mitotic (M) phase. Interphase is subdivided into:

  • G1 phase (First Gap): Cell growth and normal metabolism.

  • S phase (Synthesis): DNA replication.

  • G2 phase (Second Gap): Preparation for cell division.

The M phase includes mitosis (nuclear division) and cytokinesis (cytoplasmic division).

Mitosis: Stages and Events

Mitosis is divided into five phases:

  1. Prophase: Chromatin condenses into visible chromosomes; nucleoli disappear; mitotic spindle begins to form.

  2. Prometaphase: Nuclear envelope fragments; spindle microtubules attach to kinetochores on chromosomes.

  3. Metaphase: Chromosomes align at the metaphase plate; all kinetochores are attached to spindle fibers.

  4. Anaphase: Sister chromatids separate and move toward opposite poles; cell elongates.

  5. Telophase: Nuclear envelopes reform; chromosomes decondense; nucleoli reappear.

Cytokinesis overlaps with telophase, dividing the cytoplasm and forming two daughter cells.

Mitotic spindle and chromosomes during metaphase

Cytokinesis: Animal vs. Plant Cells

  • Animal Cells: Cleavage furrow forms, pinching the cell in two via an actomyosin ring (actin and myosin proteins).

  • Plant Cells: Cell plate forms, leading to the development of a new cell wall between daughter cells (Golgi vesicles deposit material).

Cleavage furrow in animal cell and cell plate in plant cell

Regulation of the Cell Cycle

Cell Cycle Control System

The cell cycle is regulated by a molecular control system with checkpoints at G1, G2, and M phases. These checkpoints ensure that critical processes are completed before the cell proceeds to the next phase.

  • G1 Checkpoint: Most important; if the cell receives a go-ahead signal, it continues the cycle; otherwise, it enters a non-dividing G0 phase.

  • G2 and M Checkpoints: Ensure DNA is properly replicated and chromosomes are correctly attached to the spindle.

Cyclins and Cyclin-Dependent Kinases (Cdks)

Two main types of regulatory proteins control the cell cycle:

  • Cyclins: Proteins whose levels fluctuate during the cell cycle.

  • Cyclin-Dependent Kinases (Cdks): Enzymes activated by binding to cyclins; they phosphorylate target proteins to advance the cell cycle.

  • MPF (Maturation-Promoting Factor): A cyclin-Cdk complex that triggers passage from G2 to M phase.

Signals to progress can be internal (e.g., proper spindle attachment) or external (e.g., growth factors).

External Regulation: Growth Factors and Inhibition

  • Growth Factors: Proteins released by certain cells that stimulate others to divide (e.g., PDGF).

  • Density-Dependent Inhibition: Cells stop dividing when crowded.

  • Anchorage Dependence: Cells must be attached to a surface to divide.

Loss of Cell Cycle Control and Cancer

Cancer Cells and Tumor Formation

Cancer cells do not respond to normal cell cycle controls. They may produce their own growth factors, ignore inhibitory signals, or have abnormal control systems. Uncontrolled division leads to tumor formation:

  • Benign Tumor: Abnormal cells remain at the original site.

  • Malignant Tumor: Cells invade surrounding tissues and can metastasize to other parts of the body.

Treatments include radiation (for localized tumors) and chemotherapy (for metastatic cancers), which target dividing cells.

Genetic Basis of Cancer

  • Oncogenes: Mutated genes that cause cancer by promoting uncontrolled cell division (e.g., ras gene).

  • Proto-oncogenes: Normal genes that regulate cell growth and division; mutations convert them to oncogenes.

  • Tumor Suppressor Genes: Genes that inhibit cell division (e.g., p53 gene); mutations reduce their function, leading to cancer.

Example: BRCA1 is a tumor suppressor gene; mutations increase the risk of breast and ovarian cancer.

Binary Fission in Prokaryotes

Prokaryotic cells (e.g., bacteria) divide by binary fission:

  • The chromosome replicates, and the two copies move apart.

  • The plasma membrane pinches inward, dividing the cell into two.

Summary Table: Mitosis vs. Meiosis

Feature

Mitosis

Meiosis

Chromosome Number in Daughter Cells

Same as parent (diploid)

Half of parent (haploid)

Genetic Identity

Identical to parent

Genetically unique

Function

Growth, repair, asexual reproduction

Production of gametes

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