Chapter 12 – The Cell Cycle (Campbell Biology, 10th ed.)

Key Roles of Cell Division

Fundamental distinction between living & non-living matter: ability to reproduce one’s own kind via cell division. This process is essential for the continuity of life, ensuring that genetic information is accurately passed from one generation of cells to the next.
Functions across organisms:
- Unicellular eukaryotes & prokaryotes: Cell division serves as the primary mode of reproduction for the entire organism, leading to new, independent individuals.
- Multicellular eukaryotes: Cell division plays diverse and crucial roles throughout an organism's life cycle:
  - Development (zygote ➜ adult): A single fertilized egg undergoes countless rounds of highly regulated cell division to form a complex, multicellular organism with specialized tissues and organs.
  - Growth: Increases the total number of cells in an organism, leading to an increase in size and mass from birth through maturity.
  - Tissue repair/renewal: Replaces damaged or dead cells (e.g., healing wounds, replenishing red blood cells, replacing skin cells, continuous renewal of the intestinal lining), ensuring tissue integrity and function.
Cell division is one phase within the broader cell cycle (the entire life of a cell from its formation from a dividing parent cell to its own division into two daughter cells).
Campbell Figure 12.2 illustrates three key contexts where cell division is vital:
- (a) Reproduction in unicellular species: A single amoeba dividing into two genetically identical offspring.
- (b) Growth & development of multicellular embryo: From a fertilized egg to a developing organism.
- (c) Tissue renewal: For example, continuously replacing millions of blood cells or skin cells throughout life.

Genetic Material & Chromosome Architecture

Genome = the complete set of all genetic instructions (DNA) in a cell.
- Prokaryotes: Typically possess a single, circular DNA molecule located in the nucleoid region.
- Eukaryotes: Characterized by multiple, linear DNA molecules organized into chromosomes within the nucleus.
DNA in eukaryotic cells is meticulously packaged with a large amount of proteins (primarily histones) to form chromatin. This complex undergoes significant condensation during cell division, becoming tightly packed chromosomes that are visible under a light microscope.
- During interphase, chromatin is less condensed, allowing for gene expression.
- During mitosis, chromatin condenses to prevent tangling and damage during segregation.
Chromosome numbers are species-specific and precisely maintained:
- Somatic (non-reproductive) cells: Typically contain a diploid set (2n) of chromosomes, meaning they have two sets of chromosomes, one inherited from each parent (e.g., human somatic cells have 2n = 46 chromosomes).
- Gametes (sperm/egg): Reproductive cells that contain a haploid (n) set of chromosomes, meaning they have only one set of chromosomes (e.g., human gametes have n = 23 chromosomes); these are produced by meiosis, a specialized type of cell division.
Pre-division events are critical for accurate distribution:
- DNA replication occurs during the S phase of interphase, resulting in duplicated chromosomes.
- Each duplicated chromosome consists of two identical sister chromatids, which are exact copies of the original DNA molecule. These sister chromatids are held tightly together along their lengths by protein complexes called cohesin proteins.
- Centromere = a specialized constricted region on the duplicated chromosome where the sister chromatids are most closely attached. This is also the site where kinetochore proteins will assemble.
- After the cohesins are cleaved and the sister chromatids separate during anaphase, each chromatid is then considered an independent chromosome.
Visual reference: Fig 12.4/12.5 sequence visually depicts the entire process from chromosome duplication (S phase) to their alignment during metaphase and subsequent separation during anaphase.

Overview of the Eukaryotic Cell Cycle

The eukaryotic cell cycle is divided into two broad phases:
- Mitotic (M) phase: This is the shortest part of the cell cycle and includes two major events:
  - Mitosis (karyokinesis): The division of the nucleus, resulting in two genetically identical nuclei.
  - Cytokinesis: The division of the cytoplasm, typically overlapping with the later stages of mitosis, creating two separate daughter cells.
- Interphase ( ~90%): The longest phase, characterized by intense metabolic activity and cell growth, as well as preparation for cell division. It is subdivided into three sub-phases:
  - G*1 ("first gap"): Period of initial growth, protein synthesis, and organelle production. The cell monitors its environment and decides whether to proceed with division.
  - S ("synthesis"): Critical phase where DNA replication occurs, resulting in the duplication of chromosomes. Each chromosome now consists of two sister chromatids.
  - G*2 ("second gap"): Further growth and preparation for mitosis. The cell synthesizes proteins and organelles necessary for cell division, and centrosomes complete their duplication.
- It is important to note that cell growth occurs in all three sub-phases of interphase (G1, S, and G2), but DNA replication is exclusively confined to the S phase.
German anatomist Walther Flemming (1882) pioneered the use of dyes to observe chromosomes during cell division and coined the term “mitosis,” derived from the Greek word “mitos,” meaning thread, referring to the thread-like appearance of chromosomes.

Detailed Stages of Mitosis (Dividing the Nucleus)

Mitosis is a continuous process, but for descriptive purposes, it is divided into five distinct stages:

Prophase
- Chromatin condenses: The diffuse chromatin fibers begin to tightly coil and fold, making the individual duplicated chromosomes (each composed of two sister chromatids) visible with a light microscope.
- Nucleoli disappear: Ribosome synthesis ceases, and the nucleolus vanishes as chromatin condenses.
- Mitotic spindle formation begins: The mitotic spindle, a macromolecular structure composed of microtubules and associated proteins, starts to assemble. It originates from the centrosomes (microtubule-organizing centers, each containing a pair of centrioles in animal cells) which begin to move apart towards opposite poles of the cell as pre-spindle microtubules lengthen.
Prometaphase
- Nuclear envelope fragments: The nuclear envelope breaks down into numerous small vesicles, allowing the spindle microtubules to access the chromosomes.
- Spindle microtubules penetrate nuclear space: Microtubules extend from the centrosomes into the region formerly occupied by the nucleus.
- Kinetochores form and attach: Kinetochores, specialized protein complexes, assemble on each sister chromatid at the centromere. Some spindle microtubules, called kinetochore microtubules, attach directly to these kinetochores. This attachment is crucial for chromosome movement.
- Non-kinetochore microtubules interact: Other microtubules, called non-kinetochore microtubules (or polar microtubules), do not attach to chromosomes but overlap and interact with similar microtubules from the opposite pole, contributing to cell elongation.
Metaphase
- Centrosomes at opposite poles: The two centrosomes have migrated to lie at opposite ends of the cell, forming the two poles of the mitotic spindle.
- Chromosomes align at metaphase plate: All duplicated chromosomes congregate at the metaphase plate, an imaginary plane equidistant between the two spindle poles. The centromeres of all chromosomes lie on this plate.
- Bi-orientation: Each kinetochore of a sister chromatid pair is attached to kinetochore microtubules originating from opposite poles, ensuring that the sister chromatids are under tension and properly positioned for separation.
Anaphase
- Cohesins cleaved: The cohesin proteins that hold sister chromatids together are suddenly cleaved (hydrolyzed) by an enzyme called separase. This releases the sister chromatids from each other.
- Sister chromatids separate & move to poles: Once separated, each chromatid is now considered an individual chromosome. These newly separated chromosomes are rapidly pulled toward opposite poles of the cell by the shortening of kinetochore microtubules. The shortening occurs primarily by depolymerization (loss of tubulin subunits) at their kinetochore ends, effectively