Lecture 9 | The Eukaryotic Cell Cycle and Interphase

Introduction to Cell Division

  • Importance of Cell Division

    • Enables the continuity of life.

    • The cell cycle is a series of cyclic events essential for reproduction and growth.

  • Functions

    • In unicellular organisms, each cell division produces a new organism.

    • Cell division supports the development of multicellular organisms from zygotes.

    • Serves as a repair and renewal process (e.g., skin and blood cells).

Eukaryotic Cell Cycle Phases

  • Four Main Phases

    1. G1 Phase (Gap 1)

    2. S Phase (Synthesis - DNA replication)

    3. G2 Phase (Gap 2)

    4. M Phase (Mitosis + Cytokinesis)

  • Non-dividing Cells

    • Cells may enter a quiescent state known as G0 phase.

    • Example durations in fast-dividing cells:

      • G1 Phase: ~24 hours

      • S Phase: ~30 minutes

      • G2 Phase: ~10 hours

      • M Phase: ~9 hours

Cell Cycle Control System

  • Key Points

    • Cell division must be tightly regulated; uncontrolled division leads to cancer.

    • Cell-cycle control occurs at three critical transition checkpoints:

      • G1/S

      • G2/M

      • Metaphase/Anaphase

    • Ensures completion of necessary events in each phase before progressing.

    • If requirements are not met, the cell cycle may halt, enter G0, or activate apoptosis.

Cyclins and Cyclin-dependent Kinases (Cdks)

  • Cyclin-Cdk Interaction

    • Cdks require specific cyclins for activation.

    • Cyclins are synthesized in response to signals and degrade after checkpoint progression.

    • CDKs are not destroyed but cyclically activated/deactivated by phosphorylation.

    • Checkpoint Proteins

      • Cyclin-dependent kinases drive cell cycle progression by phosphorylating target proteins (e.g., initiators of DNA replication).

G1 Phase

  • Overview

    • Metabolic activity, cell growth, and repair in preparation for division.

  • G1/S Checkpoint Decisions

    • Assess DNA integrity and determine conditions for progressing:

      • Proceed to S Phase if conditions are favorable (triggered by mitogens).

      • Delay S Phase Entry for further growth or repair.

      • Exit Cell Cycle to G0 Phase.

      • Initiate Apoptosis if DNA is severely damaged.

S Phase

  • Overview

    • DNA replication occurs; duplicated centrosome.

    • Nuclear DNA is replicated but chromosomes are not yet visible in X shape (exist as chromatin).

    • Activation of S-Cdk initiates DNA replication.

Centrosome

  • Function

    • Regulates microtubule organization; consists of two centrioles (9 triplets of microtubules).

    • Organizes microtubules during cell division, forming the mitotic spindle for accurate chromosome segregation.

G2 Phase

  • Overview

    • Rapid cell growth and protein synthesis to prepare for mitosis.

    • DNA is checked for replication and damage at G2/M checkpoint.

    • Cells enter mitosis only if DNA is fully replicated and undamaged.

M Phase Overview

  • Description

    • Continuous sequence involving several symmetric events leading to cell division.

  • Stages of M Phase

    1. Prophase: Chromatin condenses into visible chromosomes, spindle apparatus assembles.

    2. Prometaphase: Nuclear envelope disintegrates; chromosomes attach to spindle microtubules.

    3. Metaphase: Chromosomes align at spindle equator; M checkpoint ensures proper alignment.

    4. Anaphase: Cohesins break down; sister chromatids segregate to opposite poles.

    5. Telophase: Chromosomes arrive at poles, decondense, and nuclear envelopes reform.

    6. Cytokinesis: Cytoplasm divides through the contraction of a contractile ring.

Programmed Cell Death (Apoptosis)

  • Overview

    • Apoptosis is regulated cell death triggered by stimuli, maintaining balance in cell population.

  • Differences from Necrosis

    • Apoptosis is a controlled process, unlike necrosis which results from acute injury.

Apoptosis Activation

  • Mechanisms

    • Activation via internal/external signals initiating a proteolytic cascade from procaspases to caspases.

  • Pathways

    • Intrinsic: Response to stress (e.g., viral infection).

    • Extrinsic: External death signal activating procaspases through death receptors.

Apoptosis and Health

  • Balance Importance

    • Rate of cell death must balance new cell production through mitosis.

    • Either excessive or insufficient apoptosis may contribute to diseases such as cancer and neurodegenerative disorders.

Summary of Key Points

  • Eukaryotic cell cycle phases include interphase (growth and preparation), S phase (DNA replication), and M phase (mitosis and cytokinesis).

  • The cell cycle is regulated by a control system ensuring proper progression and survival signals to avoid apoptosis.