Cell Biology: Chromosome Structure and Mitosis

Chromosome Structure

• Chromosomes are composed of two sister chromatids joined at the centromere.
• The centromere is a highly constricted region of DNA where the sister chromatids are in close contact.
• Kinetochores are protein units that attach to spindle fibers and provide the attachment points for microtubules.

Mitotic Spindle

• Organizes and sorts chromosomes during mitosis.
• Formed from microtubule organizing centers (MTOCs) at centrosomes (two centrioles lying at right angles).
• There are three types of microtubules in the mitotic spindle of animal cells:
  • Aster microtubules: radiate outward from the centriole to the membrane.
  • Polar microtubules: extend between the two poles of the spindle.
  • Kinetochore microtubules: attach to the kinetochore.

Phases of Mitotic Cell Division

• Prophase:
  • Nuclear envelope breaks down.
  • Chromosomes become visible.
  • Sister chromatids are connected at the centromere.
• Prometaphase:
  • Chromosomes are clearly visible as double structures.
  • Centrioles reach opposite poles of the cell.
  • Spindle fibers form.
  • Spindle fibers attach to centromeres, specifically the kinetochores.
• Metaphase:
  • Chromosomes align on the metaphase (equatorial) plate.
• Anaphase:
  • Removal of cohesin proteins causes centromeres to separate.
  • Kinetochore microtubules shorten, pulling separated sister chromatids to opposite poles (characteristic V shape).
• Telophase:
  • Spindle fibers disappear.
  • Centrioles return to normal positioning.
  • Chromosomes uncoil.
  • Nuclear envelope reforms.
• Cytokinesis:
  • Division of the cytoplasm (cell division).
  • Produces two identical daughter cells.
  • Differs in plant and animal cells (cell plate vs. cleavage furrow).
  • Does not have to occur in all cells of all organisms (multinucleated tissue).

Cell Cycle Regulation

• Checkpoints ensure the cell can transition from one phase to another.
  • G1 checkpoint: checks cell size, the presence of molecular signals (e.g., growth factors), and DNA integrity.
  • G2 checkpoint: checks DNA integrity and verifies replication.
  • M checkpoint (spindle checkpoint): checks if all sister chromatids are correctly attached to spindle microtubules after metaphase.
• Cyclin-dependent kinases (CDKs):
  • Act as master control molecules, regulating progression through the cell cycle.
  • Only function when associated with proteins called cyclins, forming CDK-cyclin complexes.
  • Phosphorylate other proteins, activating or inactivating them at specific times in the cell cycle.
  • Different CDKs appear at specific times in the cell cycle.

Meiotic Cell Division

• More complex than mitosis.
• Basic cell cycle is the same (interphase), but the M phase is now meiosis.
• Two divisions occur:
  • Meiosis I (reductional division): reduces chromosome number from 2n to n.
  • Meiosis II (equational division): produces four haploid gametes.
• DNA synthesis occurs before the beginning of meiosis I but does not occur again before meiosis II.

Prophase I of Meiosis I

• Leptotene (leptonema): Chromatin condenses into very thin chromosomes.
• Zygotene (zygonema): Homologs search and recognize each other. Synapsis begins (synaptonemal complex forms).
• Pachytene (pachynema): Tetrad formation (homologs pair). Crossing over (recombination nodules appear).
• Diplotene (diplonema): Chiasma (chiasmata pl) remains (sections resulting from crossing over). Tetrad begins to pull apart slightly.
• Diakinesis: Nuclear envelope fragmentation and synaptonemal complex disappears.

Metaphase I of Meiosis I

• Independent assortment of nonhomologs.

Anaphase I of Meiosis I

• Homologs move to opposite sides of the cell (one half of each tetrad). Disjunction occurs (centromeres holding sister chromatids do not divide).

Aneuploidy in Humans

• Variations in chromosome number (organism gains or loses one or more chromosomes other than an exact multiple of the haploid set).
• Monosomy: Loss of a single chromosome (2n - 1). Example: Turner Syndrome (XO).
• Trisomy: Gain of a single chromosome (2n + 1).
  • Three copies of one chromosome are present, resulting in irregular pairing configurations.
  • Often lethal for autosomes, but less dramatic phenotype for sex chromosomes.
  • Examples:
    • XXX: Triple X syndrome.
    • XXY: Klinefelter syndrome.
    • XYY: Jacobs syndrome.
  • Trisomy 21 (Down syndrome): Most common genetic disorder caused by a chromosomal abnormality. 90% of cases involve an extra chromosome from the mother's egg. Familial Down syndrome is different and runs in families.
  • Other trisomies: Patau syndrome (trisomy 13) and Edwards syndrome (trisomy 18) - only 5% chance of survival beyond 1 year.
• Trisomies are frequently found in spontaneously aborted fetuses.

Non-disjunction in Meiosis

• The cause of aneuploidy.

Sex-linked Inheritance

• Genes located on one of the two sex chromosomes, but not both.
  • X-linked: Found on the X chromosome (recessive or dominant).
    • Many human disorders, including hemophilia and colorblindness.
    • Males are more likely to be affected due to hemizygosity (only one copy of X chromosome).
  • Y-linked (holandric): Found on the Y chromosome.
    • Rare, only a few genes in humans.
    • Transmitted from father to son.

Dosage Compensation

• Mammalian cells count their X chromosomes and only allow one to remain active.
• In human females, one X is inactivated, becoming highly compacted and forming a Barr body.
  • Most genes on the inactivated X cannot be expressed.
  • The inactivated X remains compacted and inactive during replication, passed on to all future somatic cells.
• Results in genetic mosaics.
  • Examples: calico cats and red-green colorblindness in humans.

Number of Barr Bodies

• Normal female (XX): 1 Barr body.
• Normal male (XY): 0 Barr bodies.
• Turner syndrome (female, XO): 0 Barr bodies.
• Triple X syndrome (female, XXX): 2 Barr bodies.
• Klinefelter syndrome (male, XXY): 1 Barr body.

Sex-limited Inheritance

• Expression of a specific phenotype is absolutely limited to one sex.
• Example: Hen-feathered and cock-feathered chickens.

Sex-influenced Inheritance

• Sex of an individual influences the expression of a phenotype that is not limited to one sex or the other.
• Example: Baldness in humans.

This quiz covers key concepts in cell biology related to chromosome structure and the phases of mitotic cell division. Explore the roles of sister chromatids, centromeres, and the mitotic spindle in the process of mitosis. Test your understanding of how these components interact during cell division.