FALL SEMESTER 2024

Instructor: Anthony Uzwiak

uzwiak@dls.rutgers.edu

Cellular Biology II

These notes dig deeper into the function of the nucleus and cell cycle.

Topics included:

1. Describe the structure and function of the nucleus and nuclear membrane

2. Describe the organization of the DNA molecule

3. Describe the stages of the cell cycle

4. Describe the differences between mitosis and meiosis

5. Describe the stages of mitosis and meiosis

6. Describe and classify the different types of neoplasia

7. Describe neoplastic transformation

8. Describe the epidemiology and etiology of cancer

Nucleus

Again—

• Nucleus: Contains genetic material— directs cell activity

  • Located near the center of the cell

  • Consists of nucleoplasm surrounded by a nuclear envelope.

    • Nuclear envelope is composed of two membranes separated by a space

    • Nuclear envelope has nuclear pores, openings where molecules move between the nucleus and cytoplasm

    • Perinuclear cisterna is the liquid between membranes

  • Deoxyribonucleic acid (DNA) is mostly found within the nucleus

• Nucleolus is a dense region within the nucleus. Subunits for ribosomes are made in the nucleolus.

  • DNA are organized into chromosomes

    • Chromatin is composed of DNA and histones to form chromosomes

  • Nucleosomes are structural units of chromosomes, consisting of DNA wrapped around protein called histones

  • Cannot leave the nucleus— DNA directs protein synthesis by ribonucleic acid (RNA) which leaves nucleus through nuclear pores

Cell Life Cycle

The cell cycle, put simply, includes the changes a cell undergoes from the time it is formed until it splits into two cells. There are two major phases of a cell’s life— interphase and cell division (mitosis).

Interphase

Interphase forms the cell formation up until cell division. Nearly all cell life is spent during interphase— during this phase, the cell carries out metabolic activities. There are three subphases to interphase.

• G1: Growth phase with little cell division related activities

  • Carries out routine metabolic activities.

• S: Synthetic phase— DNA replication occurs (synthesized).

  • DNA replication is when two DNA molecules separate, serving as the template strand for making new nucleotides.

  • One strand is continuous: called the leading strand, while the other is called the lagging strand

    • Each cell in the body (aside from sex cells) contains a specific number of chromosomes— diploid number

      • Diploid number in humans is 46

      • Sex cells have haploid number, 23, which is half of diploid number

• G2: Brief growth period for synthesizing proteins necessary for division. Cell prepares for cell division.

  • Very brief

Cell Division

Cell division is necessary for tissue repair and growth. In cell division, a parent cell divides to form into two daughter cells, each having the same DNA as the parent cell. Cell division has two major events. Mitosis and cytokinesis.

• Mitosis: division of chromosomes into new nuclei; has four phases

  • Daughter cells are identical to mother cell

  • After chromatids have been separated, daughter cells have received complementary chromosomes and are genetically identical

• Cytokinesis: division of cytoplasm into new cells

Somatic (body) cells typically have 46 chromosomes (diploid), which exist in homologous pairs (23 chromosomes). The chromosome of each pair is inherited from one male parent and one female parent.

Phases of Mitosis

1. Interphase

   1. Replication occurs. DNA organelles, and centrioles (microtubules) duplicate.

2. Prophase

   1. Centrioles move to other ends of the cell

   2. Chromatin becomes dense to make mitotic chromosomes

      1. Each copy is a chromatid, attached to the centromere (center)

      2. A protein called the kinetochore binds the centromere, providing a point of attachment for the microtubules to come and separate during mitosis

   3. Sister chromatids are connected by the centromere

   4. Nucleoli disappear

   5. Centriole pairs are

   6. Spindle fibers form and attach to kinetochore on chromosomes

3. Metaphase

   1. Chromosomes align to the center of the cell

1. Anaphase

   1. Centromeres split, chromatids separate

   2. Sister chromatids are pulled to opposite ends of the cell by the kinetochore fibers contracting

      1. Resulting in a V-shape

      2. Shortest stage of mitosis

2. Telophase

   1. Chromosome movement halts

   2. Nuclear envelope forms around the chromosomes

   3. Chromosomes uncoil back to chromatin

   4. Mitotic phase is completed

Phases of Cytokinesis

Cytokinesis is the division of the cell’s cytoplasm that begins and continues at the start of telophase (so, nearly at the end of the mitotic phase).

The first sign of cytokinesis comes from the formation of a cleavage furrow, an indentation of the plasma membrane that forms midway at the centrioles. Then, a contractile ring pulls the membrane inward forward and splits the cytoplasm into two.

Apoptosis

Meiosis

Meiosis is a specialized type of cell division for gametes (reproductive sex cells) that occurs in the ovaries or testes. Remember how somatic cells are diploid (contain 46 chromosomes)? Gametes contain the haploid number of chromosomes (23).

The end result of meiosis are four daughter cells with half the number of chromosomes from the mother cell. There are two divisions of meiosis— meiosis I and meiosis II.

Meiosis I

1. Prophase I

   1. 46 duplicate chromosomes (2 sister chromatids) connected by the centromere.

   2. Chromosomes become visible

   3. Nuclear membrane disappears

   4. Homologous pairs come together in a process called synapsis— the homologous chromosomes form tetrads.

      1. Part of the chromatid of one homologous chromosome breaks off and is exchanged with another chromatid. This is called crossing over, and results in a new genetic combination. Crossover points are called chiasmata.

1. Metaphase I

   1. Homologous pairs line up in the middle of the cell

      1. However, alignment is random. Combined with crossing over, the genetic recombination is the cause of diversity of genetic composition in sperm cells and oocytes.

2. Anaphase I

   1. Chromosomes of homologous pairs separate to opposite ends of the cell

   2. Centromeres do not break, sister chromatids remain attached

3. Telophase I

   1. New nuclei form

   2. Meiosis I is completed

At the end of meiosis I, each daughter cell still has two chromatids. These chromatids separate in meiosis II.

Meiosis II

Meiosis II is the same as mitosis, without interphase S, where chromosomes are duplicated. It contains the same stages, prophase, metaphase, anaphase, and telophase.

Cancer

Cancer is the unchecked growth of genetically abnormal cells. Cancers are broken into different classifications— origin, characteristics, and prognosis or therapy.

Origin

• Carcinoma

  • Originates from epithelial tissue

    • Glandular

    • Squamous

    • Melanocyte

• Sarcoma

  • Originates from connective tissue

    • Cartilage

    • Bone

    • Fibrous connective

    • Meninges

    • Think: co- in connective with co- in sarcoma

Characteristics

Neoplasia is a term that refers to the increase of new cells. This can lead to the formation of tumors. There are two types of tumors— benign and malignant.

• Benign Tumors

  • They resemble normal tumors, grow slowly, and do not invade other tissue

• Malignant Tumors (Cancer)

  • These are poorly differentiated tissues that grow rapidly, destroy nearby tissue, and can metastasize (spread) to other parts of the body.

Dystrophy— a disorder that arises from abnormal cell size.

• Hypertrophy is the increase of cell size.

Dysplasia— a disorder that arises from abnormal cell number.

• Hyperplasia is the increase in the number of cells.

• Aplasia is the decrease in the number of cells.

  • Both are normal during development

Prognosis or Therapy

• Tumor mass

  • Size of the tumor indicates how advanced the cancer is

• Lymph movement

  • Presence of cancer in nearby lymph nodes can indicate risk of metastasis

• Metastasis

  • Spread of cancer to other parts of the body

Epidemiology

Epidemiology is the study of disease— otherwise factors that lead to cancer. First, epidemiology focuses on risk factors.

Risk Factors

Both host and environmental factors can lead to an increased risk of cancer.

Host Factors:

• Age

• Sex

• Psychological Factors

• Genetic Factors

Environmental/Lifestyle Factors:

• Geographical location

• Nutrition

• Occupation (exposure to certain chemicals/pollutants)

  • Asbestos

  • Pesticides

  • Radiation

• Cigarette smoking

Etiology

Etiology of disease means that diseases are complex: oftentimes there is more than one single cause. It requires both:

• DNA Damage

• Inadequate physiological defense or repair

Cancer cells can form in numerous ways. Neoplastic transformation is the initiation of cancer cells.

• Arise from a single cell

• Cell suffers multiple transformation genetic mutations

  • Mutations are inherited or acquired

  • Acquired mutations

    • Random events during DNA replication

    • Induced by carcinogens (mutagens)

Initial DNA damage promotes further accumulation of future damage

• Induce cell proliferation or growth (proto-oncogenes)

• Inhibit growth of damaged cells (tumor suppressor genes)

Treatment

There are multiple different ways of cancer treatment.

• Surgery

  • First line of treatment

  • Resection of the tumor

• Radiation therapy

  • X-rays or gamma rays are delivered to the tumor; kills cancer cells

• Chemotherapy

  • Cytotoxic drugs damage the DNA of rapidly growing cancer cells

• Bone Marrow Transplantation

  • Certain cancers may require high doses of radiation therapy or chemotherapy, which can be harmful to bone marrow

• Biological response modifiers

  • Agents that boost the immune system response or antagonize tumor growth

• Gene therapy

  • Modifies gene function to repair DNA or inhibit tumor growth

Tissue

Tissue, as you may now, are a group of closely associated cells performing a similar function.

Classes of Tissue:

Nervous tissues are responsible for the chemical and electrical transmission of information.