Cell Cycle, Mitosis, and Cancer: Principles of Eukaryotic Cell Division

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Cell Cycle, Mitosis, and Cancer

Key Learning Outcomes

This section introduces the fundamental concepts of cell division, the organization of genetic material, and the regulation of the cell cycle, with a focus on the implications for cancer biology.

Why Cell Division?

Reproduction: Cell division enables organisms to reproduce asexually or sexually, ensuring the continuation of species.
Growth and Development: Multicellular organisms grow and develop from a single cell through repeated cell divisions.
Tissue Renewal: Cell division replaces old, damaged, or dead cells, maintaining tissue health.

Examples of cell division: asexual reproduction, growth and development, tissue renewal

Cellular Organization of Genetic Information

Genetic information is organized into structures called chromosomes, which are composed of chromatin—a complex of DNA and proteins. Chromatin condenses to form visible chromosomes during cell division.

Chromatin structure: chromosome, chromatin, DNA helix

Somatic Cells vs. Gametic Cells

Somatic Cells: All body cells except reproductive cells; diploid (2n), containing two sets of chromosomes.
Gametic Cells: Reproductive cells (sperm and egg); haploid (n), containing one set of chromosomes.

Chromosome Number & Ploidy

Different species have characteristic chromosome numbers. Ploidy refers to the number of sets of chromosomes in a cell.

Species	Chromosome #	Common Name
Parasitic equorum	4	Roundworm
Oryza sativa	24	Rice
Homo sapiens	46	Human
Pan troglodytes	48	Chimpanzee
Canis familiaris	78	Dog

Chromosome numbers in various species

Polyploidy in Plants

Many plants are polyploids, meaning they have more than two sets of chromosomes. Polyploidy can result in increased size and vigor.

Name	Ploidy	Chromosome Number
Common wheat	6N	42
Tobacco	4N	48
Potato	4N	48
Banana	3N	27
Boysenberry	7N	49
Strawberry	8N	56

Examples of polyploid plants

Chromosome Duplication and Structure

Before a cell divides, its chromosomes must be duplicated. Each duplicated chromosome consists of two sister chromatids joined at a centromere.

Electron micrograph of a duplicated chromosome with sister chromatids and centromeres Diagram of chromosome duplication and structure

The Cell Cycle

The cell cycle is the ordered sequence of events that a cell goes through to divide and produce two daughter cells. It consists of interphase (G1, S, G2) and the mitotic (M) phase.

G1 phase: Cell growth
S phase: DNA synthesis (replication)
G2 phase: Preparation for mitosis
M phase: Mitosis and cytokinesis

Cell cycle diagram showing G1, S, G2, and M phases

Phases of Mitosis

Mitosis is divided into several stages: prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis.

Overview of mitosis stages

Prophase: Chromosomes condense, spindle apparatus forms.
Prometaphase: Nuclear envelope breaks down, spindle fibers attach to kinetochores.
Metaphase: Chromosomes align at the metaphase plate.
Anaphase: Sister chromatids separate and move to opposite poles.
Telophase: Nuclear envelopes reform, chromosomes decondense.
Cytokinesis: Division of the cytoplasm, forming two daughter cells.

G2 of interphase and prophase Prometaphase and metaphase Anaphase and telophase/cytokinesis

Mitotic Spindle and Chromosome Movement

The mitotic spindle is a structure made of microtubules that segregates chromosomes during mitosis. Kinetochores are protein complexes on chromosomes where spindle fibers attach.

Fluorescent image of mitotic spindle Diagram of metaphase spindle Detailed diagram of spindle and microtubule attachment

Cytokinesis

Cytokinesis is the process of dividing the cytoplasm to form two separate daughter cells. In animal cells, this occurs via a cleavage furrow; in plant cells, a cell plate forms.

Diagram of telophase and cytokinesis Cleavage furrow in cytokinesis Comparison of cytokinesis in animal and plant cells

Bacterial Cell Division (Binary Fission)

Bacteria divide by binary fission, a simpler process than mitosis. The single, circular chromosome replicates, and the cell splits into two genetically identical daughter cells.

Step 1 of binary fission Step 2 of binary fission Step 3 of binary fission

Early Eukaryotic Cell Division

Some unicellular eukaryotes, such as dinoflagellates and diatoms, have unique mechanisms of cell division that differ from typical mitosis in multicellular eukaryotes.

Dinoflagellate mitosis Diatom mitosis Dinoflagellate illustration Diatom illustration

Cell Cycle Regulation

The cell cycle is tightly regulated by checkpoints (G1, G2, M) that ensure proper division. Regulatory proteins such as cyclins and cyclin-dependent kinases (Cdks) control progression through the cycle.

Cell cycle checkpoints G1 and M checkpoint diagrams Checkpoint requirements

Positive Regulation: Cyclins and Cdks

Cyclins: Proteins whose concentrations fluctuate throughout the cell cycle.
Cyclin-dependent kinases (Cdks): Enzymes that, when bound to cyclins, phosphorylate target proteins to drive cell cycle progression.

Cyclin expression cycle Cyclin-dependent kinase activation

Negative Regulation: Tumor Suppressors

Negative regulators, such as the p53 protein, halt the cell cycle in response to DNA damage or other problems, preventing the propagation of errors.

p53 normal and mutated pathways

Breakdown of Cell Cycle Regulation and Cancer

When cell cycle regulation fails, cells may divide uncontrollably, leading to cancer. Tumor suppressors (negative regulators) and proto-oncogenes (positive regulators) are key players in this process.

Tumor Suppressors: Genes that inhibit cell division; mutations can lead to loss of control.
Proto-Oncogenes: Genes that promote cell division; when mutated, they become oncogenes and drive cancer.

p53 normal and mutated pathways (duplicate for emphasis) Cancer-causing agents and proto-oncogene activation

Metastasis and Cancer Biology

Cancer cells can invade other tissues and spread throughout the body (metastasis). Studying cancer cells, such as HeLa cells, has provided insights into cell cycle regulation and cancer biology.

Comparison of Asexual and Sexual Reproduction

Asexual Reproduction: Single parent produces genetically identical offspring (clones).
Sexual Reproduction: Two parents produce offspring with unique genetic combinations.

Inheritance of Genes and Chromosome Sets

Human somatic cells have 23 pairs of chromosomes (46 total), including autosomes and sex chromosomes (XX or XY). Each pair consists of homologous chromosomes, one from each parent.

Behavior of Chromosome Sets in the Human Life Cycle

Fertilization: Union of gametes forms a diploid zygote.
Somatic Cells: Produced by mitosis from the zygote.

Meiosis and Genetic Variation

Meiosis reduces chromosome number from diploid to haploid, producing four genetically unique gametes. It consists of two divisions: meiosis I and meiosis II.

Crossing Over: Exchange of genetic material between homologous chromosomes during prophase I.
Independent Assortment: Random orientation of homologous pairs during metaphase I.
Random Fertilization: Any sperm can fertilize any egg, increasing genetic diversity.

Crossing over and synapsis during prophase I Synaptonemal complex and crossing over Independent assortment of chromosomes Crossing over produces recombinant chromosomes Random fertilization and genetic variation

Summary

Cell division is essential for reproduction, growth, and tissue maintenance.
The cell cycle is regulated by checkpoints and proteins such as cyclins, Cdks, and tumor suppressors.
Disruption of cell cycle regulation can lead to cancer.
Meiosis and sexual reproduction generate genetic diversity through independent assortment, crossing over, and random fertilization.