The Cell Cycle and Cell Division

Overview and Importance

The cell cycle is a fundamental process in all living organisms, enabling growth, development, tissue repair, and reproduction. Cell division ensures genetic continuity and is tightly regulated to maintain organismal health.

• Reproduction: Single-celled organisms reproduce by cell division; in multicellular organisms, it enables the formation of gametes.

• Growth: Cell division increases the number of cells, contributing to organismal growth.

• Regeneration: Damaged tissues are repaired through cell division.

All Cells Derive from Other Cells

Key Events in Cell Division

Cell division in all organisms involves four main events:

• Cell division signals: Initiate the process of cell division.

• DNA replication: Accurate copying of the genetic material.

• DNA segregation: Distribution of replicated DNA into daughter cells.

• Cytokinesis: Physical division of the cell into two daughter cells.

Prokaryotic Cell Division: Binary Fission

Prokaryotes, such as bacteria, divide by binary fission, a process resulting in two genetically identical daughter cells.

• Signals: External factors like nutrient availability trigger division.

• Replication: Begins at the ori (origin of replication) and ends at the ter (terminus).

• Segregation: The two ori regions move to opposite ends of the cell.

• Cytokinesis: The cell membrane pinches in, and new cell wall material forms, separating the cells.

Eukaryotic Cell Division

Eukaryotic cells divide in response to signals related to the organism's needs. The process is more complex due to multiple chromosomes and organelles.

• DNA replication: Occurs at multiple origins and is restricted to a specific cell cycle phase.

• DNA segregation: Mitosis ensures each daughter cell receives one copy of each chromosome.

• Cytokinesis: Differs between animal (membrane pinching) and plant cells (cell plate formation).

The Eukaryotic Cell Cycle Is Regulated

Phases of the Cell Cycle

The eukaryotic cell cycle consists of interphase (G1, S, G2) and the M phase (mitosis and cytokinesis).

• G1 phase: Cell grows and carries out normal functions; chromosomes are unreplicated.

• S phase: DNA replication occurs, producing sister chromatids.

• G2 phase: Cell prepares for mitosis by synthesizing necessary components.

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

Regulation of the Cell Cycle

Progression through the cell cycle is controlled by cyclin-dependent kinases (CDKs) and cyclins.

• CDKs: Protein kinases that, when activated by cyclins, phosphorylate target proteins to drive cell cycle events.

• Cyclins: Regulatory proteins whose levels fluctuate during the cell cycle, ensuring CDKs are active only at appropriate times.

Checkpoints and Control Mechanisms

Checkpoints ensure the cell cycle does not proceed if conditions are unfavorable or if DNA is damaged.

• Restriction point (R): The G1-to-S transition is a major checkpoint regulated by the retinoblastoma protein (RB).

• RB protein: Inhibits the cell cycle; phosphorylation by cyclin-CDK inactivates RB, allowing progression.

• p21 protein: Produced in response to DNA damage, inhibits CDKs, and halts the cycle for repair.

External Regulation: Growth Factors

External signals, such as growth factors, can stimulate cell division in cells that are otherwise quiescent (in G0 phase).

• Platelet-derived growth factor (PDGF): Stimulates skin cell division for wound healing.

• Interleukins and erythropoietin: Stimulate division and specialization of blood cells.

Eukaryotic Cells Divide by Mitosis

Chromosome Structure and Compaction

During mitosis, DNA is highly compacted into chromosomes, ensuring accurate segregation.

• Chromatin: DNA-protein complex; organized by histones into nucleosomes.

• Cohesins: Hold sister chromatids together after replication.

• Condensins: Further compact chromosomes for mitosis.

Phases of Mitosis

Mitosis is divided into distinct phases, each with specific events:

• 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 around daughter chromosomes.

Mitotic Spindle and Chromosome Movement

The mitotic spindle, composed of microtubules, orchestrates chromosome movement.

• Centrosomes: Organize spindle poles; replicate during S phase.

• Kinetochore microtubules: Attach to chromosomes and pull them apart.

• Motor proteins: Kinesins and dyneins move chromosomes along microtubules.

Cytokinesis

Cytokinesis divides the cytoplasm, producing two daughter cells.

• Animal cells: Contractile ring of actin and myosin pinches the cell membrane.

• Plant cells: Vesicles from the Golgi apparatus form a cell plate, which develops into a new cell wall.

Cell Death: Necrosis and Apoptosis

Necrosis

Necrosis is accidental cell death due to injury or lack of nutrients, resulting in cell swelling, bursting, and inflammation.

Apoptosis

Apoptosis is programmed cell death, essential for development and tissue homeostasis.

• Triggers: Hormones, growth factors, viral infections, toxins, or extensive DNA damage.

• Process: Cell detaches, chromatin is fragmented, cell forms blebs, and fragments are ingested by neighboring cells.

• Caspases: Proteases that hydrolyze cellular components during apoptosis.

Unregulated Cell Division and Cancer

Characteristics of Cancer Cells

Cancer cells lose normal regulatory controls, divide continuously, and can invade other tissues (metastasis).

• Benign tumors: Localized, slow-growing, and resemble parent tissue.

• Malignant tumors: Irregular, invasive, and can metastasize via blood or lymph.

Molecular Basis of Cancer

• Oncogenes: Mutated positive regulators (e.g., growth factors, receptors) that drive excessive cell division.

• Tumor suppressors: Negative regulators (e.g., RB, p53) that are inactivated in cancer cells.

• Multiple mutations: Cancer often involves several oncogenes and tumor suppressor gene mutations (e.g., Myc, Ras).

Cancer Treatments

Treatments target rapidly dividing cells and the cell cycle:

• Surgery: Removal of tumors when possible.

• Chemotherapy: Drugs like 5-fluorouracil (blocks thymine synthesis) and paclitaxel (inhibits spindle function).

• Radiation: Damages DNA, inducing apoptosis in tumor cells.

• Targeted therapy: Trastuzumab blocks HER2 receptors in some breast cancers.

Summary Table: Comparison of Prokaryotic and Eukaryotic Cell Division