Unit 3: Nucleic Acids, Cell Cycle, and Cancer

1. Nucleic Acids: Nucleosides and Nucleotides

Nucleic acids (DNA and RNA) are polymers of nucleotides. They store and transmit genetic information.

A nucleotide has three components:

1. A Pentose Sugar: Deoxyribose (in DNA) or Ribose (in RNA).
2. A Nitrogenous Base: A purine or pyrimidine.
3. A Phosphate Group: One or more phosphate groups.

Nucleoside = Sugar + Base
Nucleotide = Sugar + Base + Phosphate

[Image of the structure of a nucleoside and a nucleotide]

2. Purines and Pyrimidines

The nitrogenous bases are the "letters" of the genetic code.

• Purines (Two rings):
  • Adenine (A)
  • Guanine (G)
• Pyrimidines (One ring):
  • Cytosine (C)
  • Thymine (T) (Found only in DNA)
  • Uracil (U) (Found only in RNA)

[Image of the structures of purines (Adenine, Guanine) and pyrimidines (Cytosine, Thymine, Uracil)]

3. Physical and Chemical Properties of Nucleic Acids

a) Chemical Properties

• Phosphodiester Bonds: Nucleotides in a strand are linked by phosphodiester bonds, which connect the 5' carbon of one sugar to the 3' carbon of the next. This creates the sugar-phosphate backbone.
• Hydrogen Bonds: In DNA, the two strands are held together by hydrogen bonds between the bases.

b) Physical Properties

• UV Absorption: The nitrogenous bases strongly absorb UV light at a wavelength of 260 nm. This property is used to measure nucleic acid concentration.
• Denaturation (Melting): The two strands of DNA can be separated by heat or chemicals. The temperature at which 50% of the DNA is denatured is called the melting temperature (T_m).
  • G-C pairs (3 H-bonds) are stronger than A-T pairs (2 H-bonds). Therefore, DNA with a higher G-C content has a higher T_m.
• Renaturation (Annealing): Separated DNA strands can re-associate and re-form the double helix when cooled.

4. Double Helical Model of DNA (Watson-Crick Model)

In 1953, James Watson and Francis Crick proposed the 3D structure of B-DNA. Its key features are:

1. It consists of two polypeptide chains coiled around a common axis, forming a right-handed double helix.
2. The two strands are anti-parallel (one runs 5' → 3', the other runs 3' → 5').
3. The sugar-phosphate backbone is on the outside of the helix.
4. The nitrogenous bases are stacked on the inside, perpendicular to the helix axis.
5. The strands are held together by hydrogen bonds according to specific base-pairing rules (Chargaff's Rules):
   • Adenine (A) pairs with Thymine (T) via two hydrogen bonds.
   • Guanine (G) pairs with Cytosine (C) via three hydrogen bonds.
6. The helix has a major groove and a minor groove on its surface, which are important for protein-DNA interactions.

5. The Cell Cycle

The cell cycle is the ordered series of events that a cell passes through, leading to its division and duplication (proliferation).

[Image of the cell cycle phases (G1, S, G2, M)]

It consists of two main phases:

1. Interphase (Growth and Preparation): The longest phase, where the cell grows, carries out its normal functions, and prepares for division. It is subdivided into:
   • G₁ Phase (First Gap): Cell grows, synthesizes proteins, and carries out metabolic functions.
   • S Phase (Synthesis): DNA replication occurs. The cell copies its entire genome.
   • G₂ Phase (Second Gap): Cell continues to grow, synthesizes proteins needed for division, and checks the replicated DNA for errors.
2. M Phase (Mitotic Phase): The phase of actual cell division. It has two parts:
   • Mitosis: Division of the nucleus.
   • Cytokinesis: Division of the cytoplasm.

Some cells, like mature neurons, exit the cycle and enter a non-dividing, quiescent state called G₀.

6. Mitosis and Meiosis

a) Mitosis

Mitosis is nuclear division that results in two diploid (2n) daughter cells that are genetically identical to the parent cell. It is used for growth, repair, and asexual reproduction.

Stages of Mitosis:

1. Prophase: Chromatin condenses into visible chromosomes. The mitotic spindle begins to form.
2. Metaphase: Chromosomes (each with two sister chromatids) align at the metaphase plate (the cell's equator).
3. Anaphase: Sister chromatids separate and are pulled to opposite poles.
4. Telophase: Chromosomes arrive at the poles, decondense, and new nuclear envelopes form.

b) Meiosis

Meiosis is a special two-stage division that results in four haploid (n) daughter cells (gametes) that are genetically different from the parent cell and from each other. It is used for sexual reproduction.

• Meiosis I (Reductional Division): Separates homologous chromosomes.
  • Prophase I: Homologous chromosomes pair up (synapsis) to form bivalents. Crossing over (exchange of genetic material) occurs here.
  • Metaphase I: Homologous pairs align at the metaphase plate.
  • Anaphase I: Homologous chromosomes separate and move to opposite poles. Sister chromatids remain attached.
• Meiosis II (Equational Division): Separates sister chromatids. (This is procedurally similar to mitosis).

[Image comparing the stages and outcomes of Mitosis and Meiosis]

7. Regulation, Checkpoints, and Programmed Cell Death

a) Cell Cycle Regulation

The cell cycle is tightly controlled by a set of signaling molecules, primarily proteins called cyclins and cyclin-dependent kinases (CDKs).

• CDKs: Enzymes that are present at a constant concentration.
• Cyclins: Proteins whose concentrations fluctuate (cycle) throughout the cell cycle.

A CDK must be bound to its specific cyclin to be active. The cyclin-CDK complex then phosphorylates target proteins to drive the cell from one phase to the next.

b) Cell Cycle Checkpoints

Checkpoints are "stop-and-go" signals that pause the cell cycle to ensure all processes have been completed correctly before proceeding.

• G₁ Checkpoint: The main "restriction point." Checks for cell size, nutrients, growth factors, and DNA damage. If it fails, the cell may enter G₀ or undergo apoptosis.
• G₂ Checkpoint: Checks if all DNA has been replicated correctly and if there is any DNA damage.
• M Checkpoint (Spindle Checkpoint): Checks if all chromosomes are properly attached to the mitotic spindle before anaphase begins.

c) Programmed Cell Death (Apoptosis)

Apoptosis is a normal, controlled process of "cell suicide". It is essential for:

• Normal development (e.g., removing webbing between fingers).
• Removing damaged, infected, or potentially cancerous cells.

It is a clean process where the cell shrinks, fragments, and is engulfed by scavenger cells, without causing inflammation.

8. Cancer

Cancer is a disease characterized by uncontrolled cell proliferation. Cancer cells ignore the signals that regulate the cell cycle and division.

a) Characteristics of Cancer Cells

• Uncontrolled Growth: They divide indefinitely, ignoring checkpoints.
• Loss of Contact Inhibition: Normal cells stop dividing when they touch each other. Cancer cells pile up, forming a tumor.
• Anchorage Independence: They do not need to be attached to a surface to divide.
• Angiogenesis: They stimulate the growth of new blood vessels to supply the tumor with nutrients.
• Invasiveness: They can invade and destroy adjacent tissues.
• Metastasis: They can break away, travel through the bloodstream or lymphatic system, and form new tumors in distant parts of thebody.

b) Carcinogenesis and Promoting Agents

Carcinogenesis is the process of cancer development. It is a multi-step process involving the accumulation of mutations in genes that control the cell cycle.
Carcinogens (or agents promoting carcinogenesis) are factors that cause these mutations.

• Chemicals: e.g., components of tobacco smoke, asbestos, aflatoxin.
• Radiation: e.g., UV radiation (from the sun), X-rays, gamma rays.
• Viruses: e.g., Human Papillomavirus (HPV) (cervical cancer), Hepatitis B/C (liver cancer).

c) Oncogenes (Molecular Basis)

Two main classes of genes are involved in cancer:

1. Oncogenes:
   • These are mutated versions of normal genes called proto-oncogenes.
   • Proto-oncogenes are like the "gas pedal" of the cell cycle (e.g., they code for growth factors).
   • A mutation creates an oncogene, which is like a "gas pedal stuck to the floor," leading to constant, uncontrolled cell division.
2. Tumor Suppressor Genes:
   • These genes are like the "brakes" of the cell cycle (e.g., they code for checkpoint proteins or DNA repair enzymes).
   • A mutation *inactivates* these genes, like "losing the brakes," allowing the cell to divide even with errors.
   • A famous example is p53, which is mutated in over 50% of human cancers.

d) Treatment and Prevention of Cancer

• Treatment:
  • Surgery: Physical removal of the tumor.
  • Radiation Therapy: Uses high-energy rays to kill rapidly dividing cancer cells by damaging their DNA.
  • Chemotherapy: Uses drugs that target rapidly dividing cells throughout the body.
  • Targeted Therapy: Newer drugs that specifically target the oncogenes or proteins involved in the cancer's growth.
• Prevention:
  • Avoiding carcinogens (e.g., not smoking, using sunscreen).
  • Vaccinations (e.g., HPV, Hepatitis B).
  • Healthy diet and exercise.
  • Regular screening (e.g., mammograms, colonoscopies).