cell cycle

Chapter 12: The Cell Cycle

Introduction to Mitosis

Things to Know Before Learning About Mitosis

Understanding the structure and function of DNA is crucial in grasping the subsequent concepts surrounding mitosis.

DNA: Deoxyribonucleic Acid

Overview

DNA is the molecule that contains the instructions for life. It is composed of the following components:

  • Thymine

  • Guanine

  • Deoxyribose

Chromosomes During Mitosis

Chromosome Structure

At the start of mitosis, chromosomes condense significantly. This process involves DNA wrapping around histone proteins, which organizes the genetic material into a compact form known as chromosomes. The condensation results in:

  • DNA double helix

  • Histones (proteins)

  • Chromatin

  • Supercoiled DNA

  • Chromatid, which is half of a duplicated chromosome

Definitions

  • Chromosome: A structure made of DNA and proteins, where genes are packed tightly to be transmitted during cell division.

  • Chromatin: A less condensed form of DNA, existing in the nucleus during interphase, allowing access for transcription.

  • Nucleosome: A segment of DNA wrapped around a core of histone proteins.

  • Centromere: The region where sister chromatids are held together.

  • Telomeres: The protective caps on the end of chromosomes that do not encode genes.

Genetic Information and Related Disorders

Genes

A gene is defined as a short section of DNA found on a chromosome that codes for a protein.

Genetic Disorders

Several genetic disorders are associated with specific genes, including:

  • Malignant conditions (e.g., breast cancer, lymphoma)

  • Metabolic disorders (e.g., homocystinuria, Gaucher disease)

  • Developmental disorders (e.g., Ehlers-Danlos syndrome)

Note: The specific genetic disorders listed encompass a wide array of issues, illustrating the complexity of human genetics and the role of chromosomes in heredity.

Chromosome Visualization

Karyotypes

A karyotype is a visual representation of an individual's chromosomes. It typically shows the number and structure of chromosomes, illustrating:

  • Single Chromosomes

  • Double Chromosomes

  • Homologous chromosomes, which code for the same traits but may have variations from each parent.

The Cell Cycle

The cell cycle illustrates how a single cell divides to form two identical cells. The stages of the cell cycle include:

  1. Interphase – The cell's routine functions and growth occur here. It comprises:

    • G1 Phase (First Gap): The cell grows and performs normal metabolic processes, producing proteins.

    • S Phase (Synthesis): The cell replicates its DNA.

    • G2 Phase (Second Gap): The cell undergoes further growth and DNA repair checks.

  2. Mitosis – This stage involves the segregation of genetic material into daughter nuclei.

  3. Cytokinesis – The division of the cytoplasm and organelles into two individual cells.

  4. Binary Fission for Prokaryotes – Bacteria reproduce using this simplified method.

Importance of Cell Replacement

Cells must be replaced regularly for health, as evidenced by the following:

  • Skin cells live for approximately two weeks.

  • Red blood cells last around four months.

  • Liver cells have a lifespan of about 300-500 days.

Organelles Involved in the Cell Cycle

  • Nucleus: Houses and protects DNA.

  • Cytoskeleton: Organizes cellular components and contains centrioles that form spindle fibers essential for mitosis.

Overview of Mitosis Stages

Mitosis consists of several distinct phases:

  1. Prophase: Chromatin condenses into chromosomes; centrioles move apart; spindle fibers form and the nucleolus disassembles.

  2. Prometaphase: Centrioles are on opposite sides of the cell; DNA is completely condensed into chromosomes.

  3. Metaphase: Chromosomes align at the cell's equator; spindle fibers attach to kinetochores.

  4. Anaphase: Sister chromatids separate; motor proteins facilitate their movement.

  5. Telophase: Chromosomes reach opposite poles; nuclear membranes form around each set, and chromosomes begin decondensing.

Cytokinesis

Mechanisms

  • Animal Cells: A cleavage furrow forms through the constriction of microfilaments.

  • Plant Cells: A cell plate forms during division, derived from Golgi vesicles.

Cell Cycle Regulation

Checkpoints

Checkpoints control the progression through the cell cycle, ensuring that conditions are suitable for mitosis:

  • M Checkpoint: Ensures proper chromosome alignment before separation.

  • G1 Checkpoint: Checks cell health, nutrient availability, and need for division.

  • G2 Checkpoint: Verifies the accuracy of DNA replication prior to entering mitosis.

Internal and External Signals

Internal Signals

  • Cyclins and Cyclin-Dependent Kinases (Cdks): Cyclins regulate the progression of the cell cycle by activating Cdks, which phosphorylate target proteins necessary for cell division.

External Signals

  • Growth Factors: Stimulate nearby cells to divide.

  • Density-dependent Inhibition: Prevents overcrowding by inhibiting cell division.

  • Anchorage Dependence: Cells require adhesion to a substrate to divide.

Cancer Biology

Characteristics of Cancer Cells

Cancer cells defy normal cell cycle regulations by:

  • Producing their own growth factors.

  • Exhibiting an abnormal response to regulatory signals.

  • Forming tumors which can be either benign (localized) or malignant (metastatic).

Proto-Oncogenes and Tumor Suppressors

  • Proto-Oncogenes: When mutated, lead to uncontrolled cell division (onco-gene). Generally dominant.

  • Tumor Suppressor Genes: Their mutation prevents them from inhibiting cell division, generally recessive.

Causes of DNA Mutations

Mutations may arise from:

  • Carcinogens: Chemicals promoting cancer.

  • Radiation: High-energy radiation damaging DNA.

  • Viruses: Pathogens that alter DNA.

  • Heredity: Genetic predispositions passed from parents.

  • Random Mutations: Occur spontaneously.

HeLa Cells

Overview

HeLa cells represent the oldest and most widely used human cell line, derived from cervical cancer cells taken without consent from Henrietta Lacks. These cells are:

  • Immortal: They can divide indefinitely due to the presence of telomerase.

  • Significant in various medical research areas, including cancer treatments and vaccine development.

Ethical Concerns

The use of HeLa cells has raised ethical issues:

  • Cells were taken without informed consent.

  • Genetic material was commercialized without the family's consent, leading to public discussions on bioethics.

Conclusion

Understanding the complexities of the cell cycle, from normal cell function to cancer pathology, emphasizes the delicate balance of cellular processes and the implications of genetic research on public health and ethics.

Introduction to Mitosis

Things to Know Before Learning About Mitosis

Understanding the structure and function of DNA is crucial in grasping the subsequent concepts surrounding mitosis. DNA molecules in a cell are packaged into chromosomes.

DNA: Deoxyribonucleic Acid

Overview

DNA is the molecule that contains the instructions for life. It is composed of nucleotides, each consisting of:

  • Nitrogenous Bases:

    • Pyrimidines: Thymine (T) and Cytosine (C)

    • Purines: Adenine (A) and Guanine (G)

    • Base pairing occurs via hydrogen bonds: A pairs with T (2 bonds), and G pairs with C (3 bonds).

  • Deoxyribose: A five-carbon sugar.

  • Phosphate Group: Forms the sugar-phosphate backbone.

Chromosomes During Mitosis

Chromosome Structure

At the start of mitosis, chromosomes condense significantly. This process involves DNA wrapping around histone proteins, which organizes the genetic material into a compact form.

  • Nucleosome: The basic unit of DNA packaging, consisting of DNA wound around eight histone proteins.

  • Chromatid: One of two identical "sister" parts of a duplicated chromosome.

  • Centromere: The narrow "waist" of the duplicated chromosome, where the two chromatids are most closely attached.

  • Kinetochore: A structure of proteins attached to the centromere that links each sister chromatid to the mitotic spindle.

The Cell Cycle

The cell cycle illustrates how a single cell divides into two identical daughter cells.

  1. Interphase (90% of the cycle)

    • G_1 Phase (First Gap): Cell grows and carries out normal metabolic functions.

    • G_0 Phase: A non-dividing state occupied by cells that have left the cell cycle (e.g., nerve and muscle cells).

    • S Phase (Synthesis): DNA replication occurs; chromosomes are duplicated.

    • G_2 Phase (Second Gap): Final preparations for division; organelles double, and the cell checks for DNA errors.

  2. Mitotic (M) Phase

    • Mitosis: Division of the nucleus.

    • Cytokinesis: Division of the cytoplasm.

Detailed Stages of Mitosis

  1. Prophase: Chromatin fibers become more tightly coiled; the nucleoli disappear; the mitotic spindle begins to form.

  2. Prometaphase: The nuclear envelope fragments; microtubules extending from each centrosome can now invade the nuclear area and attach to kinetochores.

  3. Metaphase: Centrosomes are at opposite poles; chromosomes convene at the metaphase plate, an imaginary plane equidistant between the spindle's two poles.

  4. Anaphase: The shortest stage; cohesin proteins are cleaved, allowing sister chromatids to part suddenly, becoming full-fledged chromosomes moving toward opposite ends.

  5. Telophase: Two daughter nuclei form in the cell; nuclear envelopes arise from fragments of the parent cell's nuclear envelope; chromosomes become less condensed.

Cytokinesis Comparison

  • Animal Cells: Occurs by a process known as cleavage. A cleavage furrow (a shallow groove in the cell surface) forms, driven by a contractile ring of actin microfilaments and myosin.

  • Plant Cells: No cleavage furrow; instead, vesicles derived from the Golgi apparatus move to the middle of the cell, fusing to form a cell plate.

Cell Cycle Regulation and Checkpoints

The cell cycle is driven by specific signaling molecules in the cytoplasm.

  • Checkpoints: Regulatory points where stop and go-ahead signals can regulate the cycle.

    • G_1 Checkpoint: Known as the "restriction point." If a cell receives a go-ahead signal, it usually completes the whole cycle.

    • M Checkpoint: Anaphase does not begin until all chromosomes are properly attached to the spindle at the metaphase plate.

Molecular Control

  • Cyclins: Proteins that fluctuate in concentration.

  • Cyclin-Dependent Kinases (Cdks): Kinases that must be attached to a cyclin to be active.

  • MPF (Maturation-Promoting Factor): A cyclin-Cdk complex that triggers a cell's passage past the G_2 checkpoint into the M phase.

Cancer Biology and Mutations

Cancer is essentially a disease of the cell cycle where cells do not respond normally to the body's control mechanisms.

  • Transformation: The process that converts a normal cell to a cancer cell.

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

  • Malignant Tumor: Cells become invasive enough to impair the functions of one or more organs (metastasis).

  • Genetics of Cancer:

    • Oncogenes: Cancer-causing genes.

    • Proto-oncogenes: Normal cellular genes that code for proteins that stimulate normal cell growth and division. Mutations (like in the Ras gene) can turn them into oncogenes.

    • Tumor-Suppressor Genes: Proteins they encode help prevent uncontrolled cell growth (e.g., the p53 gene). Mutations in these genes act like "failed brakes."

HeLa Cells

  • Henrietta Lacks: The source of these cells in 1951.

  • Significance: HeLa cells were the first "immortal" human cell line. They have been instrumental in developing the polio vaccine, cloning, gene mapping, and in vitro fertilization.

  • Ethics: Raises modern questions about patient consent and the commercialization of biological materials.