🔄 Cell Cycle and Mitosis

Cell Cycle Overview

Cell cycle: Ordered series of events from cell formation to division

Two main phases:

1. Interphase: Cell grows and copies DNA (~90% of cycle)
2. Mitotic (M) phase: Cell divides (~10% of cycle)

Interphase

G₁ Phase (Gap 1)

• Cell grows
• Normal metabolism
• Organelle production
• G₁ checkpoint: check for size, nutrients, DNA damage

S Phase (Synthesis)

• DNA replication
• Each chromosome duplicated → sister chromatids
• Histones synthesized
• Centrosomes duplicated

G₂ Phase (Gap 2)

• Continued growth
• Protein synthesis for mitosis
• G₂ checkpoint: check for DNA replication errors

G₀ Phase

• Non-dividing state
• Some cells permanently (neurons)
• Some temporarily (liver cells)

Mitosis

Purpose: Produce two identical daughter cells

Stages: PMAT

1. Prophase

• Chromatin condenses → visible chromosomes
• Each chromosome has 2 sister chromatids (joined at centromere)
• Centrosomes move to opposite poles
• Spindle fibers begin forming
• Nuclear envelope breaks down

2. Metaphase

• Chromosomes align at metaphase plate (cell equator)
• Spindle fibers attach to kinetochores (on centromeres)
• M checkpoint (spindle checkpoint): all chromosomes attached?

3. Anaphase

• Sister chromatids separate
• Move to opposite poles
• Cell elongates

4. Telophase

• Nuclear envelopes reform around each set of chromosomes
• Chromosomes decondense
• Spindle disappears
• Cleavage furrow begins (animals) or cell plate forms (plants)

Cytokinesis

Division of cytoplasm (overlaps with telophase)

Animals:

• Cleavage furrow forms (actin/myosin ring)
• Pinches cell in two

Plants:

• Cell plate forms from vesicles
• Builds new cell wall from center outward

Cell Cycle Regulation

Cyclins and CDKs (cyclin-dependent kinases):

• Cyclins: regulatory proteins that fluctuate in concentration
• CDKs: enzymes that phosphorylate target proteins
• Cyclin-CDK complexes drive cell cycle forward

Key regulators:

• p53: "guardian of genome"
  • Stops cycle if DNA damaged
  • Triggers apoptosis if damage severe
• Rb protein: regulates G₁ checkpoint

Checkpoints:

1. G₁: size, nutrients, DNA damage
2. G₂: DNA replication complete and accurate
3. M (spindle): all chromosomes attached to spindle

Cancer and Cell Cycle

Cancer: Uncontrolled cell division

Causes:

• Proto-oncogenes mutated → oncogenes (accelerate cycle)
• Tumor suppressor genes (p53, Rb) inactivated
• Checkpoint failures

Characteristics:

• Ignore stop signals
• Don't undergo apoptosis
• Invade other tissues (metastasis)
• Induce blood vessel formation (angiogenesis)

Key Concepts

1. Interphase: G₁, S (DNA replication), G₂
2. Mitosis (PMAT): prophase, metaphase, anaphase, telophase
3. Sister chromatids separate in anaphase
4. Checkpoints ensure proper progression
5. Cyclin-CDK complexes regulate cell cycle
6. p53 stops cycle if DNA damaged
7. Cancer results from cell cycle dysregulation