Cell Cycle and Mitosis

Stages of the cell cycle, mitosis, and regulation

🔄 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

📚 Practice Problems

1Problem 1easy

❓ Question:

Describe the cell cycle phases: (a) name and describe each phase of interphase, (b) outline the stages of mitosis (M phase), and (c) explain the role of checkpoints in regulating the cell cycle.

💡 Show Solution

Cell Cycle Overview:

Interphase (90% of cycle) + M phase (10%)

(a) Interphase Phases:

G₁ Phase (Gap 1):

  • Duration: Variable (hours to years)
  • Activities:
    • Cell growth (increases in size)
    • Accumulates nutrients
    • Produces organelles, proteins
    • Normal metabolic activity
  • Commitment: Decides whether to divide
  • G₁/S checkpoint - "restriction point" or "start"

Some cells exit to G₀:

  • G₀ (Gap 0): Non-dividing state
  • Examples: Neurons (permanent), liver cells (can re-enter)

S Phase (Synthesis):

  • Duration: 6-8 hours (typical)
  • Key event: DNA replication
    • Each chromosome duplicated
    • Sister chromatids joined at centromere
    • 2n → still 2n (number of chromosomes) but DNA amount doubles
  • Histone synthesis
  • Centrosome duplication begins

G₂ Phase (Gap 2):

  • Duration: 2-5 hours
  • Activities:
    • Continued growth
    • Protein synthesis (especially for mitosis)
    • Centrosome duplication completes
    • Cell prepares for mitosis
  • G₂/M checkpoint

(b) M Phase (Mitosis + Cytokinesis):

Mitosis - Nuclear division (5 stages):

1. Prophase:

  • Chromatin condenses → visible chromosomes
  • Each chromosome = 2 sister chromatids
  • Centrosomes move to opposite poles
  • Mitotic spindle begins forming
  • Nuclear envelope starts fragmenting

2. Prometaphase:

  • Nuclear envelope completely fragments
  • Kinetochores form at centromeres
  • Spindle microtubules attach to kinetochores
  • Chromosomes begin moving

3. Metaphase:

  • Chromosomes align at metaphase plate (cell equator)
  • Kinetochores of sister chromatids attached to opposite poles
  • M checkpoint (spindle checkpoint)
  • All chromosomes must be attached before proceeding

4. Anaphase:

  • Sister chromatids separate
  • Move to opposite poles
  • Spindle microtubules shorten
  • Cell elongates
  • Now have 2n chromosomes at each pole

5. Telophase:

  • Nuclear envelopes re-form around each set
  • Chromosomes decondense
  • Spindle disassembles
  • Cleavage furrow begins (animals) or cell plate forms (plants)

Cytokinesis - Cytoplasmic division:

  • Animals: Contractile ring of actin/myosin → cleavage furrow
  • Plants: Cell plate forms from Golgi vesicles → new cell wall

Result: 2 identical daughter cells (2n each if diploid parent)

(c) Cell Cycle Checkpoints:

Purpose: Ensure proper cell division, prevent errors

G₁/S Checkpoint (Restriction Point):

  • Location: End of G₁, before S
  • Checks:
    • Is cell large enough?
    • Adequate nutrients?
    • Growth signals present?
    • DNA damage?
  • Decision:
    • ✓ Pass → Enter S phase (committed to divide)
    • ✗ Fail → Enter G₀ or undergo apoptosis

Regulation:

  • CDKs (cyclin-dependent kinases) + cyclins
  • p53 protein ("guardian of genome") - detects DNA damage
  • Rb protein (retinoblastoma) - prevents S phase entry

G₂/M Checkpoint:

  • Location: End of G₂, before mitosis
  • Checks:
    • Is DNA fully replicated?
    • Any DNA damage?
    • Cell large enough?
  • Decision:
    • ✓ Pass → Enter mitosis
    • ✗ Fail → Repair DNA or apoptosis

M Checkpoint (Spindle Checkpoint):

  • Location: Metaphase
  • Checks:
    • All chromosomes attached to spindle?
    • Kinetochores properly attached to opposite poles?
    • Proper tension on spindle fibers?
  • Decision:
    • ✓ Pass → Anaphase proceeds (APC activated)
    • ✗ Fail → Wait until all attached

Molecular control:

MPF (Maturation-Promoting Factor):

  • Cyclin + CDK complex
  • Triggers entry into M phase
  • Phosphorylates proteins needed for mitosis

Cyclin levels fluctuate:

Cyclin
 level
   ^     /\         /\
   |    /  \       /  \
   |   /    \     /    \
   |  /      \   /      \
   |_/________\_/_________> Time
     G1  S  G2 M  G1  S  G2 M

Cancer connection:

  • Mutations in checkpoint genes → uncontrolled division
  • p53 mutations: ~50% of cancers
  • Rb mutations: retinoblastoma, other cancers

Checkpoints ensure: DNA integrity, proper replication, correct chromosome attachment\boxed{\text{Checkpoints ensure: DNA integrity, proper replication, correct chromosome attachment}}

2Problem 2easy

❓ Question:

Describe the cell cycle phases: (a) name and describe each phase of interphase, (b) outline the stages of mitosis (M phase), and (c) explain the role of checkpoints in regulating the cell cycle.

💡 Show Solution

Cell Cycle Overview:

Interphase (90% of cycle) + M phase (10%)

(a) Interphase Phases:

G₁ Phase (Gap 1):

  • Duration: Variable (hours to years)
  • Activities:
    • Cell growth (increases in size)
    • Accumulates nutrients
    • Produces organelles, proteins
    • Normal metabolic activity
  • Commitment: Decides whether to divide
  • G₁/S checkpoint - "restriction point" or "start"

Some cells exit to G₀:

  • G₀ (Gap 0): Non-dividing state
  • Examples: Neurons (permanent), liver cells (can re-enter)

S Phase (Synthesis):

  • Duration: 6-8 hours (typical)
  • Key event: DNA replication
    • Each chromosome duplicated
    • Sister chromatids joined at centromere
    • 2n → still 2n (number of chromosomes) but DNA amount doubles
  • Histone synthesis
  • Centrosome duplication begins

G₂ Phase (Gap 2):

  • Duration: 2-5 hours
  • Activities:
    • Continued growth
    • Protein synthesis (especially for mitosis)
    • Centrosome duplication completes
    • Cell prepares for mitosis
  • G₂/M checkpoint

(b) M Phase (Mitosis + Cytokinesis):

Mitosis - Nuclear division (5 stages):

1. Prophase:

  • Chromatin condenses → visible chromosomes
  • Each chromosome = 2 sister chromatids
  • Centrosomes move to opposite poles
  • Mitotic spindle begins forming
  • Nuclear envelope starts fragmenting

2. Prometaphase:

  • Nuclear envelope completely fragments
  • Kinetochores form at centromeres
  • Spindle microtubules attach to kinetochores
  • Chromosomes begin moving

3. Metaphase:

  • Chromosomes align at metaphase plate (cell equator)
  • Kinetochores of sister chromatids attached to opposite poles
  • M checkpoint (spindle checkpoint)
  • All chromosomes must be attached before proceeding

4. Anaphase:

  • Sister chromatids separate
  • Move to opposite poles
  • Spindle microtubules shorten
  • Cell elongates
  • Now have 2n chromosomes at each pole

5. Telophase:

  • Nuclear envelopes re-form around each set
  • Chromosomes decondense
  • Spindle disassembles
  • Cleavage furrow begins (animals) or cell plate forms (plants)

Cytokinesis - Cytoplasmic division:

  • Animals: Contractile ring of actin/myosin → cleavage furrow
  • Plants: Cell plate forms from Golgi vesicles → new cell wall

Result: 2 identical daughter cells (2n each if diploid parent)

(c) Cell Cycle Checkpoints:

Purpose: Ensure proper cell division, prevent errors

G₁/S Checkpoint (Restriction Point):

  • Location: End of G₁, before S
  • Checks:
    • Is cell large enough?
    • Adequate nutrients?
    • Growth signals present?
    • DNA damage?
  • Decision:
    • ✓ Pass → Enter S phase (committed to divide)
    • ✗ Fail → Enter G₀ or undergo apoptosis

Regulation:

  • CDKs (cyclin-dependent kinases) + cyclins
  • p53 protein ("guardian of genome") - detects DNA damage
  • Rb protein (retinoblastoma) - prevents S phase entry

G₂/M Checkpoint:

  • Location: End of G₂, before mitosis
  • Checks:
    • Is DNA fully replicated?
    • Any DNA damage?
    • Cell large enough?
  • Decision:
    • ✓ Pass → Enter mitosis
    • ✗ Fail → Repair DNA or apoptosis

M Checkpoint (Spindle Checkpoint):

  • Location: Metaphase
  • Checks:
    • All chromosomes attached to spindle?
    • Kinetochores properly attached to opposite poles?
    • Proper tension on spindle fibers?
  • Decision:
    • ✓ Pass → Anaphase proceeds (APC activated)
    • ✗ Fail → Wait until all attached

Molecular control:

MPF (Maturation-Promoting Factor):

  • Cyclin + CDK complex
  • Triggers entry into M phase
  • Phosphorylates proteins needed for mitosis

Cyclin levels fluctuate:

Cyclin
 level
   ^     /\         /\
   |    /  \       /  \
   |   /    \     /    \
   |  /      \   /      \
   |_/________\_/_________> Time
     G1  S  G2 M  G1  S  G2 M

Cancer connection:

  • Mutations in checkpoint genes → uncontrolled division
  • p53 mutations: ~50% of cancers
  • Rb mutations: retinoblastoma, other cancers

Checkpoints ensure: DNA integrity, proper replication, correct chromosome attachment\boxed{\text{Checkpoints ensure: DNA integrity, proper replication, correct chromosome attachment}}

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