Mitosis Detailed Notes

Cell Division: Mitosis

Introduction

• Cell division is essential for reproduction in all life forms.
• In unicellular organisms (bacteria and archaea), cell division results in the reproduction of the entire organism.
• In multicellular organisms, cell division is necessary for:
  • Development from a fertilized egg.
  • Growth.
  • Repair.
• Cell division is a part of the cell cycle, which is the life of a cell from formation to division.
• Most cell divisions produce genetically identical daughter cells (clones).
• Meiosis, discussed on Wednesday, is an exception and produces sperm and egg cells that are not identical to the parent cell.

Genome and Chromosomes

• The genome is the total DNA of a cell.
• Prokaryotes typically have a single DNA molecule.
• Eukaryotes usually have multiple DNA molecules, packaged into chromosomes.
• Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein.
• Chromosomes condense during cell division and become visible.
• Each species has a characteristic number of chromosomes in each nucleus.
• Somatic cells (non-reproductive cells) have two sets of chromosomes.
• Gametes (reproductive cells: sperm and eggs) have half the number of chromosomes as somatic cells.

Chromosome Duplication and Structure

• Before cell division, DNA is replicated.
• Replicated chromosomes consist of two identical sister chromatids.
• Sister chromatids are joined copies of the original chromosome, attached along their length by cohesins (proteins acting as "glue").
• The centromere is a narrowed region where sister chromatids are most closely attached.
• During cell division:
  • Sister chromatids separate and become individual chromosomes.
  • Each new daughter cell receives one copy of each chromosome.

Mitosis and Cytokinesis

• Cell division in eukaryotic cells involves:
  • Mitosis: Division of the genetic material (DNA).
  • Cytokinesis: Division of the cytoplasm.
• Gametes are produced by meiosis, which yields non-identical daughter cells with half the chromosomes of the parent cell.

Cell Cycle Phases

• The cell cycle consists of:
  • Mitotic (M) phase: Mitosis and cytokinesis occur.
  • Interphase: Cell growth and chromosome copying in preparation for cell division.
• Interphase accounts for about 90% of the cell cycle and is divided into three subphases:
  • G1 phase (first gap phase).
  • S phase (DNA synthesis): DNA is copied.
  • G2 phase (second gap phase).
• The cell grows during all three subphases of interphase.

Mitosis Stages

Review before Mitosis

• Chromosomes have been duplicated but are not yet visible.
• The nuclear envelope surrounds the nucleus.
• Centrosomes start to appear.

Prophase

• The mitotic spindle develops.
• Chromosomes condense and become visible.
• Sister chromatids are joined together.
• Centromeres are visible as a tightening along the chromosome.

Prometaphase

• The spindle fully develops.
• Microtubules attach to the chromosomes at the centromere via kinetochores.

Metaphase

• Spindles align the chromosomes at the center of the cell, forming the metaphase plate.
• Sister chromatids are attached to the spindle.

Anaphase

• Sister chromatids separate and become daughter chromosomes.
• Daughter chromosomes are pulled to opposite ends of the cell by the spindle.
• Ensures each daughter cell gets a copy of each original chromosome.

Telophase

• The nuclear membrane reforms.
• Each end of the cell has one copy of each chromosome.
• Followed by cytokinesis to divide the cell into two daughter cells.

Mitotic Spindle

• The mitotic spindle is made of microtubules and moves chromosomes during mitosis.
• Spindle assembly begins at the centrosome (microtubule organizing center).
• Centrosomes contain centrioles.
• Microtubules extend from the centrosomes towards the chromosomes.
• Centrosomes replicate during interphase and migrate to opposite ends of the cell during prophase and prometaphase.
• The aster is an array of microtubules extending from each centrosome.
• The spindle includes the centrosomes, spindle microtubules, and asters.
• At prometaphase, spindle microtubules attach to kinetochores of the chromosomes at the centromeres and begin to move the chromosomes.
• Kinetochores are protein complexes associated with centromeres, aiding chromosome movement.

Separating Sister Chromatids

• At metaphase, chromosomes are aligned at the center of the cell.
• In anaphase, cohesins are cleaved by separase, separating sister chromatids.
• Daughter chromosomes move along kinetochore microtubules towards the poles of the cell.
• Microtubules shorten by depolymerizing at the kinetochore end.
• The kinetochore pulls the chromosome along the microtubule towards the end of the cell, breaking down the microtubule as it passes through.

Cytokinesis

• Telophase involves the formation of genetically identical daughter nuclei.

• Cytokinesis starts during anaphase or late telophase, and the spindle disassembles.

• Cytokinesis differs in animal and plant cells:

  • Animal cells: Cleavage furrow forms, pinching the cell in two.
  • Plant cells: A cell plate forms in the middle, eventually becoming a new cell wall.

• Animal cell cleavage involves a cleavage furrow contracting to separate the cell.

• Plant cell cytokinesis involves vesicles forming a cell plate that becomes a new cell wall.

Binary Fission

• Occurs in Bacteria and Archaea.
• The chromosome is copied.
• The two copies separate to opposite ends of the cell.
• The cell elongates and divides by constricting in the middle.
• FTSZ protein defines the division plate (divisome).

Evolution of Mitosis

• Eukaryotes evolved from prokaryotes; mitosis likely evolved from binary fission.
• Some protists show intermediate cell division types.
• Dinoflagellates divide chromosomes with microtubules within an intact nuclear membrane.
• Diatoms and some yeast have microtubules within the nucleus.

Cell Cycle Regulation

• Cell division frequency varies among cell types.

• The cell cycle is driven by chemical signals in the cytoplasm.

• Experiments fusing mammalian cells at different cell cycle phases support this idea:

  • Fusing an S phase cell with a G1 phase cell causes the G1 cell to enter S phase.
  • Fusing an M phase cell with a G1 phase cell causes the G1 cell to enter M phase.

• Growth factors are external signals stimulating cell division.

  • Platelet-derived growth factor (PDGF) stimulates fibroblast division.

    • PDGF is a molecule released by cells that stimulates other cells to divide
    • PDGF is made by blood cell fragments called platelets

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

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

• These inhibitions control cell growth based on cell density and attachment.

Cancer Cells

• Cancer cells do not exhibit density-dependent inhibition or anchorage dependence.

• Cancer cells may:

  • Produce their own growth factors.
  • Convey growth factor signals without growth factors.
  • Have an abnormal cell cycle control system.

• Transformation is the process converting a normal cell to a cancerous cell.

• The immune system can recognize and kill some cancer cells.

• Unrecognized cancer cells form tumors (uncontrolled cell masses).

• Benign tumors remain at the original site.

• Malignant tumors invade surrounding tissues and metastasize (spread to other body parts).

• Localized tumors are treated with high-energy radiation to damage DNA.

• Metastatic cancers are treated with chemotherapies targeting the cell cycle.