Cell Cycle, Cell Division, and Mitosis Study Notes

Cell Division, Mitosis, and the Cell Cycle

Overview of Cell Division

• Definition: Asexual reproduction producing identical cells.

  • For unicellular organisms, cell division serves as reproduction for the entire organism.

  • Examples: Prokaryotes, many eukaryotes.

  • For multicellular organisms, cell division serves multiple functions:

  • Development: From zygote to adult.

  • Growth: Increase in size.

  • Maintenance: Replace damaged or old cells.

  • Cell division occurs constantly; different cells divide on varying schedules.

Part 1: Prokaryotic Cell Division

Binary Fission

• A simpler process illustrating fundamental concepts of cell division in prokaryotes.

Steps of Binary Fission

1. Attachment and Elongation:

   • Bacterial chromosome (nucleoid) attaches to the inside of the plasma membrane.

   • The cell elongates, which increases its volume. DNA replication occurs.

2. Migration of Daughter Nucleoids:

   • Daughter nucleoids migrate to opposite sides as the cell continues to elongate.

   • The cell wall/plasma membrane begins to grow inward.

3. Cell Separation:

   • Nucleoids separate and the cell wall/plasma membrane pinches off to form two distinct cells.

Prokaryotic DNA Replication Overview

• Initiation: DNA replication begins at the origin of replication, where replication machinery moves bi-directionally.

• Progression: Replication continues until it meets at the terminus; during this phase, the nucleoid of the bacteria separates into two identical strands.

• Cell Elongation: As DNA is replicated, the bacterial cell elongates and partitions, with origins moving towards the cell wall and termini towards the center.

• Septation Process:

  • New cell membrane and bacterial cell wall material grow to form a septum at the midpoint.

  • Septation facilitated by a protein called FtsZ.

• Final Separation: Once the septum is complete, the cell pinches off completely to form two daughter cells, each containing an identical DNA copy.

Part 2: The Eukaryotic Cell Cycle and Cell Division

Definition

• Eukaryotic Cell Cycle: The ordered sequence of events in the life of a cell, from the division of a parent cell to the division of daughter cells.

  • Mitosis and cell division comprise only about 10% of the total cycle time.

Stages of the Eukaryotic Cell Cycle

1. Interphase:

   • The portion of the cycle where normal cellular functions occur, divided into three stages:

     • G1 Stage (Gap Phase 1): Cell growth and normal functioning.

     • S Stage (Synthesis): DNA replication occurs; growth slows down.

     • G2 Stage (Gap Phase 2): Further cell growth and preparation for mitosis; synthesis of required proteins, especially tubulin for microtubule assembly.

2. M Stage (Mitotic Stage):

   • Comprises mitosis and cytokinesis, ensuring the orderly distribution of genetic material and organelles into daughter cells.

Interphase Details

• In G2, chromosomes condense further, and sister chromatids appear connected at a common centromere.

• The machinery to distribute chromosomes begins to assemble.

  • Critical structures formed include centrosomes, which serve as microtubule organizing centers.

Chromosome Structure in Eukaryotes

• Each eukaryotic chromosome can contain hundreds to thousands of genes, and the arrangement varies:

  • Haploid (n): One copy of each chromosome.

  • Diploid (2n): Two copies.

  • Triploid (3n): Three copies, and so forth up to tetraploid (4n).

• Chromosomes are made of chromatin, a complex of DNA and proteins, existing in different states:

  • Heterochromatin: Not actively expressed.

  • Euchromatin: Actively expressed.

• Example: An average human chromosome consists of about 140 million nucleotides, which, if straightened out, measures approximately 5 cm in length.

Levels of Eukaryotic Chromosome Organization

1. Linear DNA: Structurally consists of a double helix with a phosphate-sugar backbone and base pairs.

2. Nucleosome Structure: DNA wrapped twice around a histone core, which is a complex of eight histone proteins plus H1 histone.

3. Complete Chromosome (Fully Packaged): Not functional until needed; structure is ready for cell division.

Organization of Chromosomes during Cell Division

• Homologous Chromosomes: Paternal and maternal copies of the same chromosome, which are not genetically identical. Each is referred to as a homologue.

• Sister Chromatids: Identical copies of a single homologue, joined together at a centromere.

• Centromere: A constricted region on the chromosome that binds specific proteins, creating a Kinetochore, which forms during cell division.

Mitosis and Cytokinesis

Phases of Mitosis

1. Early Prophase:

   • Chromosomes condense and become visible. Each chromosome is a pair of sister chromatids.

   • Nuclear envelope begins to break down.

   • The mitotic spindle starts forming at the centrioles with disassembly of the cytoskeleton.

2. Prophase:

   • Chromosomes are fully condensed but without specific orientation. The nuclear envelope is mostly broken down, and the nucleolus disappears.

   • Centrosomes migrate to opposite poles, preparing for spindle formation.

3. Prometaphase:

   • The nuclear envelope completely breaks down; centrosomes reach opposite poles.

   • Kinetochores attach at the centromeres of each sister chromatid, interacting with spindle microtubules to pull chromosomes toward the equator.

4. Metaphase:

   • Fully formed mitotic spindle with unattached polar microtubules.

   • Chromosomes align at the metaphase plate with tensions from both spindle poles.

5. Anaphase:

   • Shortest stage where centromeres divide and sister chromatids become daughter chromosomes, which move to opposite poles of the cell while the cell elongates.

6. Telophase:

   • Chromosomes decondense into chromatin, nuclear envelops reform around separated chromosomes, and the nucleolus reappears. The mitotic spindle disassembles.

   • This generally occurs concurrently with cytokinesis.

Cytokinesis

• Definition: The division of cytoplasm and distribution of organelles into daughter cells.

  • In Plant Cells: Formation of a cell plate which becomes new cell walls.

  • In Animal Cells: Formation of a cleavage furrow caused by a contractile ring of actin filaments, leading to cell separation.

Part 3: Control of the Eukaryotic Cell Cycle

Control Mechanisms and Checkpoints

• Checkpoints: Built-in stopping points in the cell cycle, where cells assess whether to proceed with division.

  • G1 Checkpoint: The most crucial checkpoint; absence of growth factors leads to entry into the G0 stage (non-dividing state).

  • G2 Checkpoint: Occurs immediately preceding mitosis.

  • Spindle Checkpoint: Happens during late metaphase; ensures chromosomes are correctly attached to the spindle.

Consequences of Control Mechanism Failure

• Cancer: Defined as the uncontrolled division of cells. Generally occurs when cell signals regulating the cycle are disregarded.

• Tumor Formation: Cells proliferate rapidly leading to benign or malignant masses:

  • Metastasis: The spread of cancer cells to other parts of the body.

• Cancer cells display immortality in culture, often evading apoptotic signals (programmed cell death).

Role of p53 Tumor Suppressor Gene

• Normal p53 Function: Monitors DNA integrity, halting the cell cycle at G1 if damage is detected, and activating repair mechanisms.

• Abnormal p53 Function:

  • If damaged DNA is not repaired, abnormal p53 allows cells to divide abnormally, leading potentially to cancer development.

  • DNA repair failures enable damaged cells to continue unsupervised division, which increases the chance of accumulating further mutations leading to malignancy.

Functions of Cell Division

Summary of Mitosis and Cytokinesis

• Mitosis involves the specific segregation of genetic material into two daughter nuclei, while cytokinesis ensures the physical separation of the cytoplasm and organelles leading to the formation of two distinct cells.