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 ensures that genetic material is accurately replicated and distributed to daughter cells. The cell cycle is fundamental to growth, development, and maintenance in multicellular organisms.

• Cell division is the process by which new cells are produced from preexisting cells, as first hypothesized by Rudolf Virchow.

• There are two main types of cell division in eukaryotes: mitosis (in somatic cells) and meiosis (in reproductive cells).

• Cytokinesis is the division of the cytoplasm, usually following mitosis or meiosis, resulting in two distinct cells.

Phases of the Eukaryotic Cell Cycle

The eukaryotic cell cycle consists of four main phases:

• G1 phase (First Gap): Cell grows, produces organelles, and performs its normal functions.

• S phase (Synthesis): DNA is replicated.

• G2 phase (Second Gap): Cell prepares for mitosis by producing proteins and organelles needed for division.

• M phase (Mitosis): Division of the nucleus and cytoplasm occurs.

Cells alternate between M phase and interphase (G1, S, and G2 phases).

Discovery of Cell Cycle Phases

• Autoradiography and radioactive labeling experiments (e.g., with thymidine) were used to identify when DNA replication occurs, leading to the identification of the S phase.

• Pulse–chase experiments revealed the existence of gap phases (G1 and G2) between S and M phases.

Chromosomes and Their Structure

Chromosome Organization

• Chromosomes are threadlike structures in the nucleus composed of DNA and proteins (histones), forming chromatin.

• Before mitosis, DNA condenses into compact chromosomes.

• Each replicated chromosome consists of two sister chromatids joined at a centromere.

• A gene is a region of DNA that codes for a particular protein or RNA.

Mitosis and Cytokinesis

Phases of Mitosis

Mitosis is divided into five phases, each with distinct events involving chromosomes, the spindle apparatus, and the nuclear envelope.

• Prophase: Chromatin condenses; spindle apparatus forms from microtubules (originating from centrosomes in animals).

• Prometaphase: Nuclear envelope breaks down; spindle fibers attach to kinetochores on chromosomes.

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

• Anaphase: Sister chromatids are pulled apart toward opposite poles by shortening of kinetochore microtubules.

• Telophase: Nuclear envelopes reform around the two sets of chromosomes; chromosomes decondense.

Microtubules in Mitosis

• Spindle fibers are composed of microtubules made from α- and β-tubulin.

• Microtubules originate from microtubule organizing centers (MTOCs), such as centrosomes in animal cells.

• During anaphase, microtubules shorten at the kinetochore end, pulling chromatids apart.

Cytokinesis

• In animal cells, a cleavage furrow forms via a contractile ring of actin and myosin, pinching the cell in two.

• In plant cells, vesicles from the Golgi apparatus form a cell plate that develops into a new cell wall between daughter cells.

Cell Division in Prokaryotes

• Binary fission is the process by which prokaryotes (bacteria) divide, similar in some respects to cytokinesis in eukaryotes.

Regulation of the Cell Cycle

Cell-Cycle Control Mechanisms

• Cell-cycle control varies by cell type and environmental conditions.

• Some cells (e.g., nerve and muscle cells) exit the cycle and enter a non-dividing state called G0.

Discovery of Cell-Cycle Regulators

• Cell fusion experiments showed that cytoplasmic factors can induce cell cycle transitions.

• Experiments with frog oocytes led to the discovery of mitosis-promoting factor (MPF), a complex that triggers mitosis.

Key Regulatory Proteins

• MPF consists of a cyclin-dependent kinase (Cdk) and a cyclin.

• Cdk is always present, but cyclin levels fluctuate, activating Cdk only when cyclin is abundant.

• MPF activity is regulated by phosphorylation and cyclin degradation (negative feedback).

Cell-Cycle Checkpoints

• Checkpoints are control points where the cell assesses whether to proceed with division.

• G1 checkpoint: Checks for cell size, nutrients, social signals, and DNA integrity (involves p53 protein).

• G2 checkpoint: Ensures DNA replication is complete and undamaged.

• Metaphase (M-phase) checkpoint: Ensures all chromosomes are properly attached to the spindle apparatus.

Cancer and the Cell Cycle

Properties of Cancer Cells

• Cancer is characterized by uncontrolled cell division, forming masses called tumors.

• Benign tumors do not invade other tissues; malignant tumors invade and spread (metastasis).

• Cancer cells often have defects in proteins that regulate cell growth (e.g., overactive growth-promoting proteins or inactive tumor suppressors).

Social Control and Cell-Cycle Regulation

• Normal cells rely on social control signals (growth factors) from neighboring cells to regulate division.

• Growth factors increase cyclin expression, activating Cdks and promoting cell cycle progression.

• Key regulatory proteins include E2F (promotes S phase) and Rb (inhibits E2F until overridden by growth signals).

How Cancer Develops

• Cancer can result from overproduction of G1 cyclin, defective Rb protein, or other failures in checkpoint control.

• There is no single cure for cancer due to its complex and variable molecular basis.

Key Terms and Definitions

• Anaphase: Phase of mitosis where sister chromatids separate.

• Apoptosis: Programmed cell death.

• Benign tumor: Non-invasive mass of cells.

• Binary fission: Prokaryotic cell division.

• Centromere: Region joining sister chromatids.

• Cyclin-dependent kinase (Cdk): Enzyme that, when bound to cyclin, regulates cell cycle transitions.

• Metastasis: Spread of cancer cells to new locations.

• p53: Tumor suppressor protein involved in DNA damage response.

• Spindle apparatus: Structure of microtubules that separates chromosomes during mitosis.

• Tumor suppressor: Gene/protein that inhibits cell division or promotes apoptosis.

Summary Table: Comparison of Mitosis and Meiosis

Key Equations and Concepts

• Negative Feedback Regulation of MPF:

• Cell Cycle Checkpoint Decision:

Example: Cancer and Cell-Cycle Checkpoints

If the p53 protein is mutated and cannot trigger apoptosis in response to DNA damage, cells with damaged DNA may continue to divide, increasing the risk of cancer.

Additional info: The cell cycle is tightly regulated to prevent uncontrolled cell division, which can lead to cancer. Understanding the molecular mechanisms of cell-cycle control is crucial for developing cancer therapies.