Unit 4: Cell Cycle and Nucleic Acids

The Cell Cycle and its Regulation

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

Phases of the Cell Cycle:

1. Interphase (The growth phase):
   • G1 (Gap 1) Phase: Cell grows in size, synthesizes proteins and mRNA.
   • S (Synthesis) Phase: DNA replication occurs. The cell duplicates its chromosomes.
   • G2 (Gap 2) Phase: Cell continues to grow and prepares for mitosis, synthesizing proteins needed for division.
2. M (Mitotic) Phase (The division phase):
   • Mitosis: Nuclear division (Prophase, Metaphase, Anaphase, Telophase).
   • Cytokinesis: Cytoplasmic division, resulting in two daughter cells.
3. G0 Phase: A quiescent (resting) state where the cell has exited the cycle and is not dividing (e.g., mature nerve cells).

Regulation of the Cell Cycle

The cycle is tightly controlled by regulator proteins. The key players are:

• Cyclins: Proteins whose concentration fluctuates (cycles) throughout the cell cycle.
• Cyclin-Dependent Kinases (CDKs): Enzymes that, when activated by binding to a cyclin, phosphorylate (add a phosphate to) target proteins to drive the cell cycle forward.

Key Concept:

CDKs are always present, but are inactive until a specific cyclin binds to them. For example, the G1/S cyclin-CDK complex triggers the S phase.

Mitosis and Meiosis

These are the two types of nuclear division in eukaryotes.

Mitosis

• Purpose: Growth, repair, asexual reproduction.
• Occurs in: Somatic (body) cells.
• Process: One round of division (Prophase, Metaphase, Anaphase, Telophase).
• Result: Two (2) daughter cells that are diploid (2n) and genetically identical to the parent cell.

Meiosis

• Purpose: Production of gametes (sperm and eggs) for sexual reproduction.
• Occurs in: Germ (sex) cells.
• Process: Two rounds of division (Meiosis I and Meiosis II).
  • Meiosis I: Separates homologous chromosomes. Crossing over (exchange of genetic material) occurs in Prophase I, creating genetic variation. This is the "reductional division" (2n → n).
  • Meiosis II: Separates sister chromatids (similar to mitosis).
• Result: Four (4) daughter cells that are haploid (n) and genetically different from the parent cell and each other.

Cell Cycle Checkpoints

Checkpoints are control points in the cell cycle where "stop" or "go-ahead" signals can regulate the cycle. They ensure that processes are completed correctly before the cell moves on.

• G1 Checkpoint (Restriction Point):
  • Checks for: Cell size, nutrients, growth factors, and DNA damage.
  • Decision: If conditions are not met, the cell may enter G0 or undergo apoptosis. This is the most important checkpoint for many cells.
• G2 Checkpoint:
  • Checks for: Completion of DNA replication (S phase) and any DNA damage.
  • Decision: If DNA is damaged or not fully replicated, the cell cycle stops to allow for repair.
• M Checkpoint (Spindle Checkpoint):
  • Checks for: Proper attachment of all sister chromatids to the spindle microtubules during metaphase.
  • Decision: Ensures that daughter cells receive the correct number of chromosomes.

Cell Senescence and Programmed Cell Death (Apoptosis)

• Cell Senescence:
  • An irreversible state of cell cycle arrest (the cell stops dividing permanently).
  • It is a response to cellular stress, such as DNA damage or the shortening of telomeres (the protective caps on the ends of chromosomes) after many divisions.
  • It is a protective mechanism against cancer.
• Programmed Cell Death (Apoptosis):
  • "Cellular suicide." An orderly, controlled process of cell self-destruction.
  • Mechanism: Mediated by enzymes called caspases. The cell shrinks, blebs, and breaks into membrane-bound apoptotic bodies, which are cleaned up by phagocytes.
  • Key Features: No inflammation (unlike necrosis, which is messy cell death from injury).
  • Purpose: Removing damaged, infected, or unnecessary cells (e.g., webbing between fingers during development).

Nucleic Acids: Nucleosides and Nucleotides

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

Building Blocks:

• Nitrogenous Base: (See next topic)
• Pentose Sugar:
  • Deoxyribose (in DNA - lacks an oxygen at the 2' carbon)
  • Ribose (in RNA - has an -OH at the 2' carbon)
• Phosphate Group: One or more phosphate groups.

• 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 types of nitrogenous bases.

• Purines (Two Rings):
  • Adenine (A)
  • Guanine (G)
  Mnemonic: Pure As Gold.
• Pyrimidines (One Ring):
  • Cytosine (C)
  • Thymine (T) - Found only in DNA
  • Uracil (U) - Found only in RNA
  Mnemonic: Pyramids are sharp, they CUT.

Physical and Chemical Properties of Nucleic Acids

• Chemical Properties:
  • Phosphodiester Bonds: Strong covalent bonds that link the 3' carbon of one sugar to the 5' carbon of the next sugar (via the phosphate group), forming the sugar-phosphate backbone.
  • N-Glycosidic Bonds: Covalent bonds that link the sugar to the nitrogenous base.
  • Hydrogen Bonds: Weaker bonds that form between complementary base pairs (A-T and G-C).
  • Acidic: The phosphate groups are acidic (pKa ~1) and are negatively charged at neutral pH.
• Physical Properties:
  • UV Absorption: The nitrogenous bases absorb UV light maximally at a wavelength of 260 nm. This is used to quantify DNA/RNA concentration.
  • Denaturation (Melting): The two strands of a DNA helix can be separated by heat or high pH, which breaks the hydrogen bonds. This is called melting. The melting temperature (T_m) is the temperature at which 50% of the DNA is denatured.
    Exam Tip: G-C pairs have 3 H-bonds, while A-T pairs have 2 H-bonds. Therefore, DNA with a higher G-C content is more stable and has a higher T_m.
  • Viscosity: Long, rigid DNA molecules make solutions highly viscous.

Double Helical Model of DNA

Proposed by James Watson and Francis Crick in 1953 (based on work by Rosalind Franklin and Maurice Wilkins).

Key Features of the (B-DNA) Model:

1. Two Strands: It is a double helix, composed of two polynucleotide strands.
2. Anti-parallel: The two strands run in opposite directions. One strand runs 5' to 3', and the other runs 3' to 5'.
3. Sugar-Phosphate Backbone: The (negatively charged) sugar and phosphate components are on the outside of the helix.
4. Bases Inside: The (hydrophobic) nitrogenous bases are stacked on the inside, perpendicular to the helix axis.
5. Complementary Base Pairing (Chargaff's Rules):
   • Adenine (A) always pairs with Thymine (T) via two (2) hydrogen bonds.
   • Guanine (G) always pairs with Cytosine (C) via three (3) hydrogen bonds.
6. Right-Handed Helix: The helix twists in a right-handed direction.
7. Major and Minor Grooves: The spacing of the backbones creates two grooves, which are important sites for proteins to bind to the DNA.