Unit 3: Nucleic Acids

Building Blocks of Nucleic Acids

Nucleic acids (DNA and RNA) are polymers made of monomers called nucleotides.

Each nucleotide has three components:

1. A Nitrogenous Base (Purine or Pyrimidine)
2. A Pentose Sugar (Deoxyribose in DNA, Ribose in RNA)
3. One or more Phosphate Groups

Nucleosides and Nucleotides

Key Definitions:

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

Example: Adenine (base) + Ribose (sugar) = Adenosine (nucleoside).
Adenosine + 3 Phosphates = Adenosine Triphosphate (ATP) (nucleotide).

Purines and Pyrimidines

These are the two classes of nitrogenous bases.

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

DNA Structure

Physicochemical Properties of Nucleic Acids

• Acidity: They are acids because of the phosphate groups, which are negatively charged at neutral pH.
• Denaturation (Melting): The two strands of DNA are held by hydrogen bonds. Heat or high pH can break these bonds, causing the strands to separate. This is called denaturation.
  • Melting Temperature (T_m): The temperature at which 50% of the DNA is denatured.
  • Because G-C pairs have 3 H-bonds and A-T pairs have 2 H-bonds, DNA with higher G-C content is more stable and has a higher T_m.
• UV Absorption: The bases strongly absorb UV light at a wavelength of 260 nm. This property is used to measure DNA concentration.

Double Helical Model of DNA (Watson-Crick Model)

This is the famous (B-DNA) structure proposed in 1953.

Key Features:

1. Two Strands: It's a double helix.
2. Anti-parallel: The two strands run in opposite directions (one 5' to 3', the other 3' to 5').
3. Backbone: A sugar-phosphate backbone is on the outside.
4. Bases Inside: The nitrogenous bases are stacked on the inside.
5. Complementary Base Pairing:
   • Adenine (A) pairs with Thymine (T) via two hydrogen bonds.
   • Guanine (G) pairs with Cytosine (C) via three hydrogen bonds.
6. Right-Handed Helix: The helix twists in a clockwise direction.
7. Grooves: Creates a Major Groove and a Minor Groove, which are important for protein binding.

Structure and Types of RNA

RNA (Ribonucleic Acid) differs from DNA in three key ways:

1. Sugar: It has Ribose (not Deoxyribose).
2. Base: It uses Uracil (U) instead of Thymine (T).
3. Structure: It is usually single-stranded.

Main Types of RNA:

• Messenger RNA (mRNA): Carries the genetic code from DNA (in the nucleus) to the ribosome (in the cytoplasm) to be translated into a protein.
• Transfer RNA (tRNA): Acts as an "adapter" molecule. It reads the code on the mRNA (via its anticodon) and carries the corresponding amino acid to the ribosome.
• Ribosomal RNA (rRNA): The main component of ribosomes. It acts as an enzyme (a ribozyme) to catalyze the formation of peptide bonds.

Cell Cycle and Regulation

Phases of the Cell Cycle

The cell cycle is the ordered series of events a cell goes through to duplicate its DNA and divide.

• Interphase (Growth Phase):
  • G1 (Gap 1): Cell grows and performs its normal functions.
  • S (Synthesis): DNA replication occurs. Chromosomes are duplicated.
  • G2 (Gap 2): Cell grows more and prepares for division.
• M (Mitotic) Phase:
  • Mitosis: Nuclear division.
  • Cytokinesis: Cytoplasmic division.
• G0 Phase: A non-dividing, "resting" state.

Regulation and Checkpoints

The cell cycle is tightly controlled by regulator proteins, primarily Cyclins and Cyclin-Dependent Kinases (CDKs).

• Checkpoints are "stop" signals that ensure one phase is complete and correct before starting the next.
  • G1 Checkpoint: The main "restriction point." Checks for cell size, nutrients, and DNA damage.
  • G2 Checkpoint: Checks if all DNA was replicated correctly and if there is any damage.
  • M (Spindle) Checkpoint: Checks if all chromosomes are properly attached to the mitotic spindle before anaphase.

Cancer and Carcinogenesis

Definition: Cancer

Cancer is a disease of uncontrolled cell division. It is caused by mutations in genes that regulate the cell cycle, leading to the formation of tumors.

Carcinogenic Agents

Carcinogens are agents that cause mutations in DNA, leading to cancer.

• Chemical Carcinogens: e.g., components of tobacco smoke, asbestos.
• Physical Carcinogens: e.g., UV radiation (sunlight), X-rays (ionizing radiation).
• Biological Carcinogens: e.g., Oncogenic viruses like HPV (Human Papillomavirus) and Hepatitis B.

Oncogenes and Tumor Suppressor Genes

Cancer is caused by mutations in two main types of genes.

• Oncogenes: Mutated versions of normal genes (proto-oncogenes) that promote cell growth. Example: ras.
• Tumor Suppressor Genes: Genes that normally inhibit cell division or trigger apoptosis (cell death). Example: p53 ("the guardian of the genome").

Molecular Basis of Cancer

Cancer develops in a multi-step process. A single mutation is not enough. It requires the accumulation of multiple mutations in genes that control...

• Self-sufficiency in growth signals.
• Insensitivity to anti-growth signals.
• Evading apoptosis (programmed cell death).
• Limitless replicative potential (activating telomerase).
• Sustained angiogenesis (growth of new blood vessels).
• Tissue invasion and metastasis (spreading to new sites).

Treatment and Prevention of Cancer

• Treatment:
  • Surgery: Physical removal of the tumor.
  • Radiation Therapy: Uses high-energy rays to kill cancer cells.
  • Chemotherapy: Uses cytotoxic drugs that target rapidly dividing cells.
• Prevention:
  • Avoiding carcinogens (e.g., not smoking).
  • Diet, exercise, and sun protection.
  • Vaccinations (e.g., HPV vaccine).
  • Regular screenings for early detection.