In-depth Notes on the Cell Cycle

Cell Cycle Overview

• Definition: The cell cycle encompasses the life of a cell from its formation until it divides, integral to processes like reproduction, growth, and repair of tissues.

Organization of DNA

• DNA organization occurs before cell division to ensure effective replication and separation.
• Histones: Proteins that DNA wraps around to form nucleosomes.
• Nucleosomes: Basic unit of DNA packaging.
• Chromatin: A form of DNA that is less condensed when the cell is not dividing.
• Chromosomes: Formed from condensed chromatin post-DNA replication, allowing easier organization for cell division.

Structure of Chromosomes

• Sister Chromatids: Two identical copies of a chromosome connected at the centromere.
  • Centromere: Region where sister chromatids are joined most tightly.
  • Kinetochore: Protein complex that attaches sister chromatids to the mitotic spindle.

Genetic Material

• Genome: Total genetic material within a cell.
  • Prokaryotes: Contain one circular DNA molecule.
  • Eukaryotes: Have multiple linear chromosomes (e.g., Humans: 46 chromosomes).
• Homologous Chromosomes: Chromosomes with the same structure and gene sequence, one inherited from each parent.

Types of Cells

• Somatic Cells: Body cells that are diploid (2n) carrying two sets of chromosomes (e.g., Humans: 2n=46).
• Gametes: Reproductive cells that are haploid (n) with one set of chromosomes (e.g., Humans: n=23).

Cell Cycle Phases

• The cell cycle consists of alternating interphase and mitotic phase (M phase).
• Interphase: 90% of the cycle, with three phases:
  • G1: Gap phase, normal functions and growth.
  • S: DNA synthesis and chromosome duplication.
  • G2: Second gap for final growth and preparation for mitosis.
• M Phase: Includes mitosis (nuclear division) and cytokinesis (cytoplasm division), resulting in two diploid daughter cells.

Stages of Mitosis

1. Prophase: Chromatin condenses, nucleoli disappear, and mitotic spindle forms.
2. Prometaphase: Nuclear envelope breaks down; microtubules attach to kinetochores.
3. Metaphase: Chromosomes align at the metaphase plate; microtubules are attached to kinetochores.
4. Anaphase: Sister chromatids separate and move to opposite poles; cell elongates.
5. Telophase/Cytokinesis: Nuclei form at each pole, nucleoli reappear; chromosomes de-condense; cytokinesis occurs (cleavage furrow in animals, cell plate in plants).

Chromosome Tracking During Mitosis

• Chromosome Count: Human cells (2n=46) track chromatid arrangements through various mitosis phases:
  • Prophase: 46 chromosomes, 92 chromatids
  • Metaphase: 46 chromosomes, 92 chromatids
  • Anaphase: 92 chromosomes, 92 chromatids
  • Telophase: 46 chromosomes (in each daughter cell).

Regulation of the Cell Cycle

• Checkpoints: Ensure proper progression through the cell cycle, reacting to internal and external signals.
• G1 Checkpoint: Assesses cell size, growth factors, and DNA integrity. A "go" signal allows the cycle to continue; a "stop" signal leads to quiescence (G0 phase).
  • G0 Phase: Cells can remain inactive indefinitely or be re-activated.
• G2 Checkpoint: Verifies DNA replication and repairs DNA damage before mitosis.
• M (Spindle) Checkpoint: Checks microtubule attachment at kinetochores; ensures the cell only progresses through mitosis if all chromosomes are properly attached.

Internal Regulators

• Cyclins: Vary in concentration across the cell cycle and regulate cyclin-dependent kinases (CDKs).
• CDKs: Consistent concentrations that become active only in combination with specific cyclins, phosphorylating target proteins to advance cell cycle events.

External Regulators

• Growth Factors: Hormones stimulating cell growth, activating CDK pathways.
• Contact Inhibition: Prevents the cell cycle from progressing if cells are in contact with each other.
• Anchorage Dependence: Cells require attachment to other cells or the extracellular matrix to divide.

Cancer and Cell Cycle Dysregulation

• Cancer arises from mutations in DNA affecting growth regulation, often leading to uncontrolled division and evasion of apoptosis.
  • Tumors: Abnormal cell masses; benign (localized) vs. malignant (invading other tissues).
• Prevention: Healthy lifestyle, avoiding carcinogens, and regular screenings.

Chemotherapy and Cell Cycle

• Vinblastine: Chemotherapeutic agent that inhibits microtubule formation, impacting mitosis phases and effectively arresting the cell cycle.