Lecture Notes: Cell Cycle and Division

Overview

• Average Human Height: ~5 feet (~2 meters)
• Smallest Unit of Life: Cell (~100 micrometers in diameter)
• Comparison: Cell is about 1/1,000,000th the size of a human

Cell Growth and Division

• Cell Lifecycle: Described by the cell cycle
• Comparison: Similar to seasons in a year
• Main Phases: Interphase and Mitosis

Interphase

• Description: Period of cell growth, not division
• Time Spent: Most of the cell's life
• Exception: Cancer cells (tend to divide more than grow)
• Subphases:
  • G1 Phase (Growth 1):
    • Longest phase
    • Production of organelles (ribosomes, proteins)
  • S Phase (Synthesis):
    • DNA replication (23 pairs of chromosomes duplicated to 46 pairs)
  • G0 Phase (Resting Phase):
    • Cells do not divide (e.g., neurons)
  • G2 Phase (Growth 2):
    • Preparation for mitosis
    • Production of microtubules (for anaphase)

Mitosis

• Description: Period of active cell division
• Abbreviation: Often abbreviated as "M"

Cell Cycle Continuation

• Post-Mitosis: Cells re-enter G1 phase
• Cycle Pattern: Cells continue to grow, prepare, and divide unless they enter G0 phase

Regulation of the Cell Cycle

Key Checkpoints

• G1 to S Phase: Regulation before DNA replication.
• G2 to Mitosis: Regulation before the cell division step.

Cyclin-Dependent Kinases (CDKs)

• Function: Add phosphate groups (+) to other enzymes or proteins, activating or inactivating them.
• Activation: CDKs require specific cyclin proteins to be active.
• Presence: CDKs are always present in cells but are usually inactive without cyclins.

Cyclins

• Definition: Proteins that activate CDKs.
• Production: Specific cyclins are produced at specific times during the cell cycle.

Cyclin-CDK Complexes and Their Roles

• G1 Phase:
  • Cyclin D and E are produced.
  • CDK-2 binds with Cyclin E.
  • CDK-4 binds with Cyclin D.
  • The CDK-4/Cyclin D complex phosphorylates RB protein, inactivating it and allowing DNA replication.
• S Phase:
  • Cyclin A is produced and complexes with CDK-2.
  • This complex activates DNA replication.
• G2 Phase:
  • Cyclin B is produced.
  • Cyclin B complexes with CDK-1.
  • This complex activates mitosis (cell division).

Importance of Cyclin Proteins

• Checkpoint Passing: Cyclin proteins are crucial for passing checkpoints as they inhibit proteins blocking DNA synthesis and promote proteins needed for mitosis.

Lecture Notes: Cell Cycle Regulation and Tumor Suppressor Genes

Key Proteins in Cell Cycle Regulation

RB Protein

• Role: Initial mention as part of higher-level regulation.
• Association: Produced from a tumor suppressor gene.

p53 (Guardian of the Genome)

• Importance: Nicknamed "guardian of the genome."
  • Named "Molecule of the Year" by Science Magazine in 1993.
  • Highlighted as more important than theobromine (chocolate).
• Function: Binds DNA to produce proteins that block cell cycle progression.
  • Key Protein Produced: p21
    • Role: Inhibits CDK (Cyclin-Dependent Kinase).
    • Effect: Prevents activation of DNA replication and mitosis.

p21

• Produced by: p53 binding to DNA.
• Function: Inhibits CDK.
• Unusual Characteristic: Does not lead to cancer when defected.
  • Unique Finding: Mice without p21 can regenerate limbs (arms and legs).

Tumor Suppressor Genes

• Definition: Genes producing proteins that regulate cell cycle and prevent uncontrolled division.
• Critical Proteins: p53 and RB
• Importance: Defected or mutated tumor suppressor genes can lead to cancer.
  • Key Term: Loss of function.

Cancer Association

• p53: Over 50% of tumors have a defect in p53.
• RB: Defect leads to retinoblastoma (eye tumor).

Summary

• Tumor Suppressor Genes: Essential for regulating the cell cycle.
• Cell Division: Requires careful regulation due to high energy and protein machinery needs.
• Future Discussion: Importance of timing in cell division; mitosis requires significant resources.

Lecture on Cell Division: Mitosis and Meiosis

Introduction

• Zygote: The initial fertilized cell from which an organism develops.
• Cell Division: Process through which a single cell divides to form many cells.
  • Two Types: Mitosis and Meiosis.

Mitosis

• Purpose: To produce two identical clones of the original cell, each with the same number of chromosomes.
• Phases of Mitosis:
  1. Interphase:
  • DNA replication occurs, forming bivalent chromosomes.
  • Bivalent chromosomes consist of two sister chromatids attached at the centromere.
  2. Prophase:
  • Bivalent chromosomes condense.
  • Mitotic spindle forms and nuclear envelope dissolves.
  3. Metaphase:
  • Chromosomes line up at the cell's center.
  • Mitotic spindles attach to chromatids.
  4. Anaphase:
  • Chromatids are separated and pulled to opposite sides of the cell.
  • Results in two groups of monovalent chromosomes.
  5. Telophase:
  • Membranes form around chromosome groups.
  • Mitotic spindles disassemble.
• Cytokinesis: The cell splits into two, each with 46 monovalent chromosomes.

Meiosis

• Purpose: To produce four genetically unique gametes (sperm or eggs) with half the chromosome number of the original cell.
• Difference from Mitosis: Gametes have half the number of chromosomes and are not clones of the original cell.

Chromosomes

• Definition: Thread-like structures made of DNA and histone proteins.
  • Chromatin: Material composing chromosomes.
  • Histones: Structural proteins around which DNA is wound.
• Chromosome Structure:
  • Average chromosome is much longer than the cell nucleus but is compacted to fit inside.
• Species-Specific Chromosome Numbers:
  • Humans: Diploid number is 46; haploid number is 23.
  • Nematodes: Diploid number is 4; haploid number is 2.
• Chromosome Terms:
  • Diploid Number: Total number of chromosomes in non-gamete cells.
  • Haploid Number: Total number of chromosomes in gametes.
  • Bivalent Chromosome: Two sister chromatids.
  • Monovalent Chromosome: One chromatid.

Summary

• Mitosis ensures genetic continuity by creating identical cells.
• Meiosis ensures genetic diversity by creating unique gametes with half the chromosome number.
• Chromosomes carry genetic information and are tightly packed within the cell nucleus.

Note: Errors in chromosome segregation can lead to genetic disorders like Down syndrome.

Cell Life Cycle: Interphase

Overview

• Interphase is where a cell spends most of its life.
• Consists of growth, DNA replication, and preparation for division.
• Followed by mitosis, a shorter phase for cell division.

Phases of Interphase

• G1 Phase (First Gap Phase)

  • The cell grows and synthesizes proteins.
  • Takes in nutrients from the environment.

• S Phase (Synthesis Phase)

  • DNA replication occurs.
  • Each chromosome replicates to form two sister chromatids connected at the centromere.
  • Centrosome duplicates.

• G2 Phase (Second Gap Phase)

  • Further cell growth and preparation for mitosis.
  • Ensures all genetic material is correctly replicated and the cell is ready for division.

Key Points

• Chromatin vs. Chromosome

  • Chromosomes are in chromatin form (unwound) during interphase, making them difficult to see under a simple microscope.

• Centrosome and Centromere

  • Centrosome: Organelle important for mitosis.
  • Centromere: Region where sister chromatids are connected.

Transition to Mitosis

• At the end of the G2 phase, the cell is ready for mitosis, where the nucleus divides into two nuclei.

Diagram Summary

1. New Cell: Begins interphase.
2. G1 Phase: Cell grows.
3. S Phase: DNA and centrosome replicate.
4. G2 Phase: Further growth and preparation.
5. Ready for Mitosis.

Mitosis and Cell Division

Overview of Interphase

• Interphase: Bulk of a cell's life cycle
  • Cell grows and DNA replicates
  • Cell grows more

Introduction to Mitosis

• Mitosis: Process where one nucleus turns into two nuclei, each with original genetic information
• Cytokinesis: Splits each nucleus into a separate cell by dividing the cytoplasm

Phases of Mitosis

Prophase

• End of Interphase: Cell with replicated DNA and two centrosomes
• Events:
  • Chromosomes condense from chromatin form to visible form
  • Nuclear membrane starts to disappear
  • Centrosomes migrate to opposite sides of the cell
• Remark: Process occurs through chemical and thermodynamic reactions

Metaphase

• Events:
  • Nuclear membrane is gone
  • Chromosomes line up at the cell's center
  • Centrosomes are at opposite ends of the cell
  • Microtubules extend from centrosomes to centromeres of chromosomes
• Centrosomes & Centrioles: Centrioles exist inside centrosomes (two per centrosome)

Anaphase

• Events:
  • Microtubules pull sister chromatids apart towards opposite centrosomes
  • Chromatids are now considered independent chromosomes
• Kinetochore: Point where microtubules connect to chromatids/chromosomes

Telophase

• Events:
  • Chromosomes start to unwind back to chromatin form
  • Nuclear membranes form around separated DNA
  • Cell membrane starts to pinch in preparation for cytokinesis

Cytokinesis

• Description: Final division of the cytoplasm resulting in two separate cells
• Process: Often considered to begin in anaphase and conclude after telophase

Conclusion

• Each resulting cell from mitosis enters Interphase
• Cycle continues with these cells growing and eventually undergoing mitosis again

Lecture Notes: Mitosis vs Meiosis

Overview

• High-level comparison of mitosis and meiosis

Mitosis

• Starting Point: Cell with diploid number of chromosomes (2n)
  • For humans: 46 chromosomes (23 from each parent)
• Process:
  • DNA replication and cell growth during interphase
  • Division into two cells each with diploid chromosomes (2n)
• Outcome:
  • Two genetically identical cells
  • Cells can re-enter the cell cycle and undergo mitosis repeatedly
• Significance:
  • Mechanism for growth and maintenance in multicellular organisms
  • Somatic cells undergo mitosis

Meiosis

• Starting Point: Cell with diploid number of chromosomes (2n)
  • DNA replication during interphase
• Meiosis I:
  • Division into two cells with haploid number of chromosomes (n)
  • Homologous chromosomes are separated randomly
• Meiosis II:
  • Further division into four haploid cells
  • Resembles mitosis but starts with haploid cells
• Outcome:
  • Four genetically diverse gametes (sex cells)
  • Not a cycle; gametes used in fertilization
• Significance:
  • Production of gametes for sexual reproduction
  • Takes place in germ cells (testes in males, ovaries in females)

Key Differences

• Mitosis: Somatic Cells
  • Results in two identical diploid cells
  • Continuous cycle
• Meiosis: Germ Cells
  • Results in four diverse haploid gametes
  • Not a continuous cycle; leads to formation of new organism upon fertilization

Lecture on Meiosis

Introduction

• Mitosis vs. Meiosis
  • Mitosis: Used for general cell division, producing genetically identical daughter cells.
  • Meiosis: Produces gametes (sperm and eggs) with half the number of chromosomes (haploid) compared to the original cell (diploid).

Phases of Meiosis

• Two-Step Division: Meiosis includes two rounds of division—Meiosis I and Meiosis II.
  • Meiosis I: Separation of homologous chromosomes.
  • Meiosis II: Separation of sister chromatids.

Meiosis I

• Interphase: Cell grows (G phase), copies chromosomes (S phase), and prepares for division (G phase).
• Prophase I:
  • Chromosomes condense and pair up with their homologues.
  • Crossing over occurs, where homologous chromosomes exchange segments of DNA.
  • Synaptonemal Complex: Protein structure that holds homologues together during crossing over.
  • Chiasmata: Cross-shaped structures where homologues are linked together.
• Metaphase I:
  • Homologue pairs line up at the metaphase plate.
  • Orientation of pairs is random, leading to genetic diversity.
• Anaphase I: Homologues are pulled apart to opposite ends of the cell.
• Telophase I: Chromosomes arrive at opposite poles, and cytokinesis usually occurs, forming two haploid daughter cells.

Meiosis II

• No DNA Replication: Cells move to Meiosis II without copying DNA.
• Prophase II: Chromosomes condense, nuclear envelope breaks down, spindle forms.
• Metaphase II: Chromosomes line up individually along the metaphase plate.
• Anaphase II: Sister chromatids separate and move to opposite poles.
• Telophase II: Nuclear membranes form, chromosomes decondense, and cytokinesis occurs.
• Outcome: Four haploid cells, each with one chromatid per chromosome.

Genetic Variation in Meiosis

• Crossing Over: Random exchange of genetic material at different points on homologues.
• Random Orientation: Homologous pairs line up randomly, allowing for many possible combinations of gametes.
• Infinite Variability: Combined effects of crossing over and random orientation create virtually infinite genetic diversity in gametes.

Meiosis I Detailed Explanation

Prophase I

• Similarities to prophase in mitosis:
  • Nuclear envelope starts to disappear.
  • Chromosomes condense into dense form.
• Unique features:
  • Chromosomal crossover occurs between homologous chromosomes.
  • Adds variation to genetic information.

Metaphase I

• Chromosomes line up along the middle of the cell.
• Centrosomes play a significant role.
• Nuclear membrane is gone.
• Microtubules attach to kinetochores on chromosomes.
  • Move chromosomes via chemical and thermodynamic processes.

Anaphase I

• Chromosomes pulled apart, but not sister chromatids.
• Homologous pairs get pulled apart.
  • Adds more genetic variation.
• Microtubules and centrosomes involved in moving chromosomes.

Telophase I

• Cytokinesis begins (cell division).
• Homologous pairs fully split and unravel into chromatin state.
• Nuclear membrane reforms.
• Microtubules dissolve.
• Results in 2 haploid cells, each with 2 chromosomes (each chromosome has 2 sister chromatids).

Key Points

• Meiosis I: Transition from diploid germ cell to two haploid cells.
• Cytokinesis in Telophase I results in two cells, each with a haploid number of chromosomes.
• Meiosis II will further split sister chromatids, similar to mitosis.

Meiosis II Overview

Introduction

• Completion of Meiosis I leads to Meiosis II.
• There may be an interphase II (rest period) between the two phases, depending on the cell type and species.

Phases of Meiosis II

Prophase II

• Begins with two cells from the end of Meiosis I.
• Nuclear envelope dissolves.
• Chromosomes condense.
• Each cell has duplicated centrosomes, which migrate to opposite ends.
• Similar to prophase in mitosis.

Metaphase II

• Centrosomes migrate to the poles.
• Nuclear membrane disappears.
• Chromosomes line up along the equator.
• Microtubules push centrosomes apart and attach to chromosomes at the kinetochores.
• Similar to metaphase in mitosis.

Anaphase II

• Sister chromatids are split and pulled to opposite poles, becoming daughter chromosomes.
• Microtubules are involved in moving chromosomes.
• Similar to anaphase in mitosis.

Telophase II

• Two cells start to become four cells.
• Chromosomes start to unravel into chromatid form.
• Nuclear envelope reforms.
• Microtubules dissolve.
• Cytokinesis occurs, resulting in four haploid cells (gametes).
• Each gamete has a haploid number of chromosomes (two chromosomes per cell).

Conclusion

• Meiosis II is analogous to mitosis because it preserves the chromosome number.
• Resulting gametes have the potential to fuse with other gametes during fertilization to create a diploid organism.
• These cells are now ready for sexual reproduction.

Lecture on Cellular Behavior, Mutations, and Cancer

Normal Cellular Process

• Daily Functioning: Most cells in the human body operate in a normal, respectable manner.
• Mitosis: Cells replicate through mitosis to replace dead cells.
• Contact Inhibition: Cells stop growing when they sense crowding.
• Apoptosis: Cells self-destruct if they recognize internal defects.

Mutations and Cell Replication

• Mutation Frequency: Mutations are relatively infrequent but do occur.
• New Cells: Approximately 100 billion new cells are created daily, leading to around 100,000 mutations per day.
• Mutations Effect: Most mutations are minor; severe ones trigger apoptosis.
• Germ Cells vs. Body Cells: Mutations in body cells do not affect offspring; germ cell mutations do.

Complexity of Human Cells

• Cell Count: Human body has approximately 100 trillion cells.
• Function and Complexity: Cells are complex ecosystems with organelles and membranes.
• Replication Variability: Some cells replicate more frequently than others.

Neoplasms and Tumors

• Neoplasm: A mass of cells from one original cell that keeps duplicating abnormally.
• Tumor: A noticeable lump of neoplastic cells.
  • Benign Tumor: Non-harmful lump that does not invade surrounding tissues.
  • Malignant Tumor: Invasive, rapidly growing lump that infiltrates surrounding tissues; can metastasize to other body parts.

Cancer Development

• Mutation Effects: Mutations can prevent apoptosis and increase replication speed.
• Invasiveness: Cancer cells invade and crowd out healthy tissues.
• Metastasis: Cancer cells can break away and spread to other body parts.
• Genetic Abnormalities: Cancer cells often have broken DNA replication systems, leading to further mutations.

Challenges in Treating Cancer

• Diverse Mutations: Cancer is not a single disease but a class of mutations.
• Treatment Difficulty: Targeting one mutation might not be effective for all cancer cells due to their variability.
• Common Treatment: Chemotherapy and radiation target fast-growing cells but do not specifically cure cancer.

Summary

• Cancer is a result of broken mitosis and DNA replication.
• Healthy cells either self-destruct or do nothing when mutations occur.
• Cancer cells avoid apoptosis and replicate uncontrollably, invading the body and using up resources.
• Understanding the cellular basis of cancer helps in appreciating the complexity and difficulty in treating the disease.