Lecture 3

Cummings 2: pp 23-33

MITOSIS

I. Cell cycles

II. Mitosis

III. The human chromosome set

Terms

A. The two major parts of the nuclear cycle are division (symbolized by M) and interphase. [Note: Fig. 2.10, p. 23, and line 1, p. 24, indicate cytokinesis as a third component of the cell cycle. However, most cytologists distinguish between the nuclear cycle (interphase + M) and the division of the cell to form two cells (cytokinesis).]

B. Interphase is divided into three parts:

1. G₁ is the period after the previous cell division up to the beginning of DNA replication.

2. S is the period of DNA synthesis.

3. G₂ is the period between DNA synthesis and the beginning of cell (nuclear) division.

C. Cell cycles are highly regulated and vary enormously depending on the cell and tissue type.

1. Many cells, such as those of the central nervous system, have no potential to divide once development is complete. They are permanently in G₁, often called the G₀ state.

2. Other cells retain their potential to divide, replacing dead cells. E.g. skin, blood.

3. Very rare cells escape regulation and grow without limit, e.g. tumors, including cancer.

II. Mitosis is the form of cell division that is characteristic of somatic cells and of gonial cells.

A. Each of the daughter cells receives a set of chromosomes that is identical to the parental set.

B. The major stages of chromosomal division and transmission are as follows:

1. Interphase refers to the period in which cell division is not active. Chromosomes are highly dispersed (although still intact) and cannot be observed microscopically. The nuclear envelope is well defined.

2. Prophase is defined as the beginning of cell division when chromosomes first become visible. Chromosomes first appear as very long thin threads that become visibly double as prophase proceeds. They continue to condense into short fat structures. The nuclear envelope disappears.

3. Metaphase occurs after prophase and is the point of maximal chromosomal condensation. The two chromatids are still attached at the centromere, which is undivided, giving the chromosomes an "X-shaped" appearance. The chromosomes align on a plane in the center of the cell (the equatorial plane or metaphase plate). Clusters of microtubules originate from the poles of the cell, forming a spindle-shaped structure with the axis perpendicular to the metaphase plate. Many of the spindle fibers are attached to the centromeric regions of the chromosomes.

4. Anaphase follows metaphase and is the period when the centromeres divide and the spindle fibers shorten, pulling the newly formed chromosomes toward the poles. The two new sister chromosomes go to opposite poles. The separation of chromosomes, either homologs or sister chromosomes, is called disjunction.

5. In telophase, the chromosomes uncoil and become disperse, and new nuclear envelopes form, producing two new nuclei at opposite ends of the cell. The cytoplasm divides between them (cytokinesis), and two new daughter cells are formed.

C. Significance of mitosis.

1. Cells in culture usually can undergo only a finite number of divisions.

2. In Werner syndrome, the number of cell divisions is reduced. The gene that is defective in Werner syndrome functions, when normal, in DNA replication and repair. It is not known whether the aging process seen in Werner syndrome is a speeded-up version of normal aging, although there are many similarities between the two processes.

III. Examination of human chromosomes is an important procedure in medical practice, since visible chromosomal abnormalities are found in many conditions.

A. All cells in the body have the same complement of chromosomes, with the exception of mature red blood cells, sperm, and ova. Therefore, chromosome observations based on one cell type apply to all other cell types.

B. Metaphase cells are used primarily, since chromosomes are maximally condensed and more readily observable.

C. Usually, lymphocytes (white blood cells) are tested. They can be induced to grow in the laboratory, producing many mitoses.

D. Fibroblasts are cell types found in most tissues and can be cultured from small skin biopsies

E. Once suitable metaphases are located on a stained slide with a microscope, they are photographed, cut out, and arranged into a standard karyotype.

F. Various staining procedures show up characteristic banding patterns on chromosomes, making it possible to identify each chromosome.

G. Human autosomes are numbered 1 through 22, starting with the longest. A normal karyotype consists of a total of 46 chromosomes: 22 autosomal pairs and a pair of sex chromosomes, either XX or XY.

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