The Cell Cycle: Mechanisms, Regulation, and Cancer

The Cell Cycle

Overview of the Cell Cycle

The cell cycle is the series of events that cells go through as they grow and divide. It is fundamental to the continuity of life, allowing organisms to reproduce, grow, and maintain their tissues.

• Cell division produces genetically identical daughter cells in most cases.

• The cell cycle alternates between the mitotic phase (M phase) and interphase.

• A molecular control system regulates the eukaryotic cell cycle.

Purpose of Cell Division

• Reproduction: In unicellular organisms, cell division reproduces the entire organism.

• Growth and Development: In multicellular organisms, cell division enables development from a single cell and growth into an adult.

• Tissue Renewal: Cell division replaces, renews, or repairs cells in multicellular organisms.

Genetic Material and Chromosome Organization

DNA Structure and Function

DNA (deoxyribonucleic acid) is the hereditary material in all cells, composed of two antiparallel strands held together by hydrogen bonds between complementary bases.

• Base pairing: Adenine (A) pairs with Thymine (T); Guanine (G) pairs with Cytosine (C).

• All the DNA in a cell is called its genome.

• Prokaryotes typically have a single DNA molecule; eukaryotes have multiple DNA molecules.

Chromosomes and Chromatin

• DNA is packaged into chromosomes, which are made of chromatin (DNA + protein).

• Chromosomes can be condensed (tightly wound) or uncondensed (loosely packed).

• Each eukaryotic species has a characteristic number of chromosomes (e.g., humans have 46 in somatic cells).

Somatic Cells vs. Gametes

• Somatic cells (non-reproductive) have two sets of chromosomes (diploid).

• Gametes (sperm and eggs) have one set of chromosomes (haploid).

• Humans: Somatic cells have 46 chromosomes; gametes have 23.

Chromosome Duplication and Sister Chromatids

• Before division, chromosomes are duplicated, forming two sister chromatids joined at the centromere.

• During division, sister chromatids separate and are considered individual chromosomes.

Phases of the Cell Cycle

Main Phases

• Mitotic (M) phase: Includes mitosis (nuclear division) and cytokinesis (cytoplasmic division).

• Interphase: Period of cell growth and DNA replication; subdivided into:

  • G1 phase (first gap): Cell grows.

  • S phase (synthesis): DNA is replicated.

  • G2 phase (second gap): Cell prepares for division.

• Interphase accounts for about 90% of the cell cycle.

Mitosis

Phases of Mitosis

Mitosis is conventionally divided into five phases, followed by cytokinesis. The process ensures equal distribution of genetic material to daughter cells.

• Prophase: Chromosomes condense; centrosomes migrate; mitotic spindle forms; nucleolus disappears.

• Prometaphase: Chromosomes fully condensed; nuclear envelope breaks down; spindle microtubules attach to kinetochores.

• Metaphase: Chromosomes align at the metaphase plate; spindle fully formed.

• Anaphase: Sister chromatids separate and move to opposite poles; cell elongates.

• Telophase: Chromosomes decondense; nuclear envelope and nucleolus reform.

• Cytokinesis: Division of the cytoplasm; cleavage furrow in animal cells, cell plate in plant cells.

Status of Nuclear Membrane and Spindle During Mitosis

• Prophase: Nuclear envelope intact, spindle forming.

• Prometaphase: Nuclear envelope fragments, spindle attaches to chromosomes.

• Metaphase: Nuclear envelope gone, chromosomes aligned, spindle fully formed.

• Anaphase: Chromatids separate, spindle pulls them apart.

• Telophase: Nuclear envelope reforms, spindle disassembles.

The Mitotic Spindle

• Composed of microtubules and proteins; organizes and separates chromosomes.

• In animal cells, spindle forms from centrosomes (microtubule organizing centers).

• Each centrosome forms an aster (radial array of microtubules).

• Plant cells lack centrioles; spindle forms near the nuclear membrane.

• Kinetochores are protein complexes at centromeres where spindle fibers attach.

• During anaphase, kinetochore microtubules shorten, pulling chromatids apart.

• Non-kinetochore microtubules elongate the cell by sliding past each other.

Cytokinesis

• In animal cells: Occurs by cleavage, forming a cleavage furrow.

• In plant cells: Occurs by formation of a cell plate.

Comparison of Cytokinesis in Animal and Plant Cells

Feature	Animal Cells	Plant Cells
Mechanism	Cleavage furrow	Cell plate formation
Structure Involved	Actin microfilaments	Vesicles from Golgi apparatus
Result	Two separate cells	New cell wall between cells

Cell Division in Prokaryotes: Binary Fission

• Prokaryotes (bacteria and archaea) divide by binary fission.

• Single chromosome replicates at the origin of replication.

• Daughter chromosomes move apart as the cell elongates.

• Plasma membrane pinches inward, dividing the cell.

Evolution of Mitosis

• Mitosis likely evolved from binary fission.

• Some protists show intermediate forms of cell division.

Regulation of the Cell Cycle

Control Systems and Checkpoints

The eukaryotic cell cycle is regulated by a molecular control system with checkpoints that ensure proper division.

• Checkpoints: Control points where the cell cycle can be stopped until conditions are favorable.

• Main checkpoints: G1, G2, and M.

G1 Checkpoint

• Most important for many cells.

• Checks for cell size, nutrients, energy, DNA integrity, and chemical signals.

• If passed, cell usually completes the cycle; if not, enters G0 phase (non-dividing state).

G2 Checkpoint

• Checks for DNA damage and proper DNA replication before mitosis.

M Checkpoint

• Checks for proper attachment of chromosomes to the spindle.

• Anaphase begins only when all kinetochores are attached.

• Activation of separase enzyme allows sister chromatids to separate.

Internal and External Signals

• Internal signals: Cytoplasmic factors can drive cell cycle progression (e.g., experiments with fused cells).

• External signals: Growth factors (e.g., PDGF) stimulate cell division; density-dependent inhibition and anchorage dependence regulate division in animal cells.

Cancer and the Cell Cycle

Loss of Cell Cycle Control in Cancer

• Cancer cells do not respond to normal regulatory signals.

• May produce their own growth factors or have abnormal signaling pathways.

• Transformation: Conversion of a normal cell to a cancerous cell.

• Cancer cells can form tumors:

  • Benign tumors: Remain at original site.

  • Malignant tumors: Invade tissues and can metastasize (spread to other sites).

Treatment of Cancer

• Localized tumors: Treated with high-energy radiation (damages cancer cell DNA).

• Metastatic tumors: Treated with chemotherapy (drugs that interfere with the cell cycle).

• Side effects of chemotherapy result from effects on normal dividing cells.

Summary Table: Key Events in Mitosis

Phase	Main Events	Nuclear Envelope	Spindle Status
Prophase	Chromosomes condense, spindle forms	Intact	Forming
Prometaphase	Envelope fragments, spindle attaches	Fragmenting	Attaching to kinetochores
Metaphase	Chromosomes align at plate	Absent	Fully formed
Anaphase	Sister chromatids separate	Absent	Shortening, pulling chromatids
Telophase	Chromosomes decondense, envelope reforms	Reforming	Disassembling

Key Terms and Definitions

• Genome: All the genetic material in a cell.

• Chromatin: DNA-protein complex making up chromosomes.

• Centromere: Region where sister chromatids are most closely attached.

• Mitotic spindle: Structure of microtubules that separates chromosomes.

• Kinetochore: Protein complex at centromere for spindle attachment.

• Binary fission: Prokaryotic cell division mechanism.

• Growth factor: Protein that stimulates cell division.

• Density-dependent inhibition: Cells stop dividing when crowded.

• Anchorage dependence: Cells must be attached to a surface to divide.

• Transformation: Conversion of normal cell to cancerous cell.

• Metastasis: Spread of cancer cells to distant sites.

Example: Platelet-Derived Growth Factor (PDGF)

• PDGF is released by platelets and stimulates division of fibroblasts in wound healing.

Additional info:

• Some protists have unique mitosis mechanisms, supporting the evolutionary link between binary fission and mitosis.

• Cell cycle checkpoints are regulated by cyclins and cyclin-dependent kinases (CDKs), though not detailed in these notes.