Mitosis and Cell Division

• Mr. Hernandez presents Mitosis in the context of Cell Division

Why Cells Divide

• Cells divide for growth, repair, and reproduction.
• Organisms grow through the addition of cells.
• Multicellular organisms have specialized cells performing different functions which arise through cell division.
• Differentiation is a process through which cells become different.
• Specialized animal cells cannot form an entire organism under normal conditions.
• Plant cells are totipotent and can be developed into a full plant.
• Cell membrane size is the most limiting factor in cell division.
• Cells must obtain nutrients.
• Volume increases more rapidly than the cell surface area.
• Larger cells need a larger surface area to survive.

Cell Cycle

• Cell cycle consists of a sequence of phases in the life of a cell.
• The stages include G1, S, G2, Mitosis, and Cytokinesis.
• The cell "double checks" the duplicated chromosomes for error, making any needed repairs during the G2 phase.
• During the S phase, each of the 46 chromosomes are duplicated by the cell.
• Cellular contents, excluding the chromosomes, are duplicated in the G1 phase.
• Cell cycle arrest occurs during the G0 phase

Cancer Genes

• These drive the uncontrolled growth and cell division leading to cancer when mutated or overexpressed.
• They come from normal genes called proto-oncogenes, which regulate cell growth and division.

Examples of Cancer Genes

• RAS gene family (KRAS, NRAS, HRAS) relates to cell signaling pathways for growth.
• HER2 (ERBB2) relates to a growth factor receptor that pertains to breast cancers.
• MYC represents a transcription factor that promotes cell proliferation.

Tumor Suppressor Genes

• These normally prevent uncontrolled cell growth by repairing DNA
• They can induce cell cycle arrest and initiate apoptosis, also know as programmed cell death.
• Loss or inactivation of tumor suppressor genes can contribute to cancer.

Examples of Tumor Suppressor Genes

• TP53 (p53), also known as the "guardian of the genome," plays a critical role in DNA repair and apoptosis.
• RB1 regulates cell cycle progression.
• BRCA1/BRCA2 is involved in DNA repair; mutations are linked to breast and ovarian cancers.

DNA Repair Genes

• These are responsible for repairing DNA damage.
• Mutations in these genes can lead to genetic instability and increase the risk of cancer.

Examples of DNA Repair Genes

• MLH1, MSH2, MSH6, PMS2 are mismatch repair genes associated with Lynch syndrome, also known as hereditary colorectal cancer.
• ATM is involved in detecting DNA damage and activating repair pathways.
• Cancer arises when mutations accumulate in these genes, disrupting the balance of cell growth and death.
• Mutations may be inherited (germline mutations) or acquired (somatic mutations) because of environmental factors.
• Cancer treatments target specific oncogenes or exploit vulnerabilities in tumor suppressor gene pathways.

Chromosome Anatomy

• A chromosome consists of two identical chromatids.
• One chromatid is an exact copy of the other and each contains one DNA molecule.
• The short arm structure is called the p arm.
• The centromere is the constricted point of the chromosome.
• q arm is the long arm structure.
• DNA molecule is a long string like DNA molecule formed into a compact structure by proteins called histones.

Terminology Associated With Mitosis

• Chromatin is a thin fibrous form of DNA and histone proteins.
• Sister chromatids are identical structures that result from chromosome replication, formed during S phase.
• Haploid cell, are cells with half the number of chromosomes, such as sex cells (sperm and egg).
• Diploid cell are cells with a complete set of chromosomes (one which is paternal and the other maternal), such as somatic cells (non-sex cells).
• In humans, the diploid cell number is 46 and the haploid number is 23.
• A cell cycle includes 2 parts: Growth and Preparation, and then the Cell Division.
• The growth and preparation phase is called interphase, (interphase= G₁ + S + G₂).
• Cell division includes: Mitosis (nuclear division) and Cytokinesis (cytoplasm division).

Interphase

• Interphase occurs before cell division.
• It is the longest part of cycle.
• It has 3 stages: G₁, S, and G₂.
• Daughter cells enter the G1 stage after cytokinesis.
• The cell will grow and multiply organelles and perform many of its specific biochemical functions.
• The G0 phase is the phase in the cell cycle in which the cell is neither dividing nor preparing for division.
• After maturity, nerve and heart cells do not divide again so they stay in the G0 phase.
• DNA replicates during the S, or Synthesis of DNA stage.
• During G2, the cell prepares for mitosis.
• The enzymes needed for cell division are made during G2.
• At the G2 phase, the cell finishes growing.
• During G2, centrosomes appear in the cytoplasm by the nucleus.
• Mitosis begins after G2 and ends before G1

Mitotic Spindle Apparatus Components

• Astral microtubule
• Centrosome with centriole pair
• Kinetochore microtubule
• Polar microtubule
• Sister chromatids
• Poles

Prophase

• During prophase, the nucleolus disappears.
• Chromatin highly condenses into chromosomes.
• The classical chromosome structure appears and becomes visible under a light microscope.
• The nuclear membrane is broken down.
• Microtubules strands or spindle fibers are growing from the centrosome.
• Microtubules strands or spindle fibers attached to a protein structure, also called a kinetochore.
• The kinetochore is located at the centromere of each sister chromatid.
• The mitotic spindle is completely formed.

Metaphase

• During metaphase, chromosomes are aligned at the center of cell.
• They line up along " the metaphase plate."
• Both chromatids face toward opposite poles of the cell and are now ready to be separated.

Anaphase

• During anaphase, microtubules attached to the kinetochore shorten and pull sister chromatids apart to each pole.
• The poles of the cell move farther apart contributing to the separation of the sister chromatids.
• Precise alignment is critical to division.
• At the end of anaphase, the sister chromatids have moved to opposite ends of the cell.

Telophase (Final Phase of Mitosis)

• Chromosomes uncoil back to chromatin.
• Nuclear envelopes form around chromatin in 2 steps.
• Nucleoli reappears in 2 phases.
• The mitotic spindle apparatus is broken up.
• Cytoskeleton forms again.
• Cleavage furrow starting to appear.
• Two new distinctive daughter cells are now visible.

Cytokinesis

• It involves the splitting of the cytoplasm:
• In animals: plasma membrane is pinched off by forming a cleavage furrow.
• In plants: the cell elongates and the cell plate forms out of vesicles (future cell wall and cell membrane).
• Main organelles are replicated (mitochondria, Golgi body and rough endoplasmic reticulum or ER).
• In the end, the cell divides into two genetically identical diploid daughter cells.