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Genes and Proteins

• Proteins do the work of the cell: growth, maintenance,

response to the environment, reproduction, etc.

• Proteins are chains of amino acids. The sequence of

amino acids in each protein is coded in the DNA as a

specific sequence of A, C, G and T bases: a gene.

• Each gene codes for a different protein.

• Key points:

– All cells within an organism have the same genes.

– What makes cells different from each other is that different genes

are turned on and turned off in different cells.

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Mitosis

• Cells divide to make more cells. While all the other organelles can be

randomly separated into the daughter cells, the chromosomes must be

precisely divided so that each

daughter cell gets exactly the same DNA.

• Mitosis is normal cell division, which goes on throughout life in all parts of the body. Meiosis is the special cell division that creates the sperm and eggs, the gametes. We will discuss meiosis separately.

• Mitosis and meiosis occur in eukaryotes. Prokaryotes use a different method—”fission” to divide. • Humans have 46 chromosomes, 23

from each parent. Every cell has the same 46 chromosomes Each species has a characteristic number of

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Chromosomes

• The essential part of a

chromosome is a single very long strand of DNA. This DNA contains all the genetic information for

creating and running the organism.

• The DNA is supported and neatly packaged by proteins bound to it. At different times, these proteins cause the DNA to be spread out like spaghetti in a bowl, or tightly condensed into the X-shaped chromosomes we can see in the microscope.

• Each chromosome has a central constricted region called a

centromere that serves as an

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More Chromosomes

• Chromosomes exist in 2 different states, before and after they

replicate their DNA. Before replication, chromosomes have one chromatid. After replication, chromosomes have 2 sister

chromatids, held together at the centromere. Each chromatid is one piece of DNA with its

supporting proteins.

• In mitosis, the two chromatids of each chromosome separate, with each chromatid going into a

daughter cell.

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Cell Cycle

• Some cells divide constantly: cells in the embryo, skin cells, gut lining cells, etc. Other cells divide rarely or never: only to replace themselves.

• Actively dividing cells go through a cycle of events that results in mitosis. Most of the cycle was called “interphase” by the microscopists who first studied cell division. During interphase the cell increases in size, but the chromosomes are invisible.

• The 3 stages of interphase are called G1, S, and G2.

• The S phase (“Synthesis”) is the time when the DNA is replicated, when the chromosome goes from

having one chromatid to having 2 chromatids held together at the centromere.

• G1 (“Gap”) is the period between mitosis and S, when each chromosome has 1 chromatid. Cells spend mot of their time in G1: it is the time when the cell grows and performs its normal function. Control of cell division occurs in G1: a cell that isn’t destined to divide stays in G1, while a cell that is to divide enters the S phase.

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Machinery of Mitosis

• The chromosomes are pulled apart by the spindle, which is made of microtubules. The

spindle fibers are attached to each centromere (which is part of the chromosome), and anchored on the other end to a centrosome (which is the organizing center for the spindle).

• There are 2 centrosomes, one at each end of the spindle. The chromosomes are lined up

between the poles of the spindle. • When the spindle fibers contract,

the chromosomes are pulled to the opposing poles.

• The cell then divides to separate the two poles.

• Stages of mitosis: prophase,

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Prophase

• In prophase, the cell begins the process of division.

• 1. The chromosomes condense. The proteins attached to the DNA cause the chromosomes to go from long thin

structures to short fat one, which makes them easier to pull apart.

• 2. The nuclear envelope disappears. The double membrane that surround the nucleus dissolves into a collection of

small vesicles, freeing the chromosomes to use the whole cell for division

• 3. The centrosomes move to opposite poles. During interphase, the pair of centrosomes were together just outside the nucleus. In prophase they separate and move to opposite ends of the cell. • 4. The spindle starts to form, growing

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Metaphase

• Metaphase is a short

resting period where the

chromosomes are lined

up on the equator of the

cell, with the centrosomes

at opposite ends and the

spindle fibers attached to

the centromeres.

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Anaphase

• In anaphase, the

centromeres divide. At

this point, each individual

chromosome goes from:

– 1 chromosome with 2

chromatids

– to:

– 2 chromosomes with one

chromatid each.

• Then the spindle fibers

contract, and the

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Telophase

• In telophase the cell

actually divides.

• The chromosomes are at

the poles of the spindle.

• The spindle disintegrates

• The nuclear envelope

re-forms around the two sets

of chromosomes.

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Cytokinesis

• The organelles (other than the

chromosomes) get divided up into the 2 daughter cells passively: they go with whichever cell they find

themselves in.

• Plant and animal cells divide the cytoplasm in different ways.

• In plant cells, a new cell wall made of cellulose forms between the 2 new nuclei, about where the chromosomes lined up in metaphase. Cell

membranes form along the surfaces of this wall. When the new wall joins with the existing side wall, the 2 cells have become separate.

• In animal cells, a ring of actin fibers (microfilaments are composed of actin) forms around the cell equator and

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Summary of Mitosis

• Prophase:

• Chromosomes condense • Nuclear envelope disappears

• centrosomes move to opposite sides of the cell

• Spindle forms and attaches to centromeres on the chromosomes

• Metaphase

• Chromosomes lined up on equator of spindle • centrosomes at opposite ends of cell

• Anaphase

• Centromeres divide: each 2-chromatid chromosome becomes two 1-chromatid chromosomes

• Chromosomes pulled to opposite poles by the spindle

• Telophase

• Chromosomes de-condense • Nuclear envelope reappears

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Cancer

• Cancer is a disease of uncontrolled cell division. It starts with a

single cell that loses its control mechanisms due to a genetic

mutation. That cell starts dividing without limit, and eventually kills

the host.

• Normal cells are controlled by several factors.

– Normal cells stay in the G1 stage of the cell cycle until they are given a specific signal to enter the S phase, in which the DNA replicates and the cell prepares for division. Cancer cells enter the S phase without

waiting for a signal.

– Normal cells are mortal. This means that they can divide about 50 times and then they lose the ability to divide, and eventually die. This “clock” gets re-set during the formation of the gametes. Cancer cells escape this process of mortality: they are immortal and can divide endlessly.

– Normal cells that suffer significant chromosome damage destroy

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Cancer Progression

• There are many different forms of cancer, affecting different cell types and working in different ways. All start out with mutations in specific genes called

“oncogenes”. The normal, unmutated versions of the oncogenes provide the control mechanisms for the cell. The mutations are caused by radiation, certain chemicals (carcinogens), and various random events during DNA replication.

• Once a single cell starts growing uncontrollably, it forms a tumor, a small mass of cells. No further progress can occur unless the cancerous mass gets its own blood supply. “Angiogenesis” is the process of developing a system of small arteries and veins to supply the tumor. Most tumors don’t reach this stage. • A tumor with a blood supply will grow into a large

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Cancer Treatment

• Two basic treatments: surgery to remove the tumor, and radiation or

chemicals to kill actively dividing cells.

• It is hard to remove all the tumor cells. Tumors often lack sharp

boundaries for easy removal, and metastatic tumors can be very

small and anywhere in the body.

• Radiation and chemotherapy are aimed at killing actively dividing

cells, but killing all dividing cells is lethal: you must make new blood

cells, skin cells, etc. So treatment must be carefully balanced to

avoid killing the patient.

• Chemotherapy also has the problem of natural selection within the

tumor. If any of the tumor cells are resistant to the chemical, they

will survive and multiply. The cancer seems to have disappeared,

but it comes back a few years later in a form that is resistant to

chemotherapy. Using multiple drugs can decrease the risk of

References

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