Cell Reproduction: Mitosis and Cancer
February 6, 2002
Cell
Reproduction: Mitosis and Cancer
February 6, 2002
Readings: Starr
Ch. 12, 196-197, Ch. 8, 126-133,
and Essay 8.6 (p 135)
CD-ROM: excellent diagrams and a cool mitosis movie!
Don't Forget! This week's WarmUp is due TODAY at 9:30!
"To understand the things that are at our door is the best preparation for understanding those things that lie beyond"- Hypatia, c. 370-415
I. Cell Division: How does one cell become two cells?
Life is based on the ability of cells to reproduce, or make copies of themselves. This is done by a process called cell division = one cell divides into two cells.
II. The Cell Cycle: How does the cell spend its time?
A cell spends a good part of its "life" working and growing, breaking down sugars, synthesizing proteins, enzymes, and other macromolecules. However, cells wear out, break down and suffer injuries. In addition, as organisms grow and change, they need new cells to make more skin tissue, bone tissue, muscle tissue. These new cells can only come from one place...(aka The Cell Theory)...other cells!
At such times, the cell makes preparations for reproduction, or cell division, where 1 cell will divide to form 2 "daughter" cells, and the whole process will start over again!
Phases of the Cell Cycle
G1 Growth of cell, development of organelles, making and breaking of macromolecules, repairing wounds, sorting proteins, cellular work. Also called "Gap 1". S Synthesis DNA replication - the cell makes a copy of each of its chromosomes, in preparation for cell division (mitosis). G2 Growth (more) and more preparation for cell division. Also called "Gap 2". M Mitotis distribution of the replicated chromosomes to two cells
Some terms:
Chromosomes: are found in the nucleus of cells and are made of DNA - repeating sequences of bases (A,T,C,G) - coiled tightly around histone proteins. An individual chromosome is one, l...o...n...g... DNA molecule which is highly coiled and condensed. The total number bases in all the chromosomes ONE human cell is approximately three billion (3,000,000,000); individual chromosomes range from 30 to 150 million base pairs EACH.Humans have 23 pairs of chromosomes, (46 total, one originally from mom and one from dad). Each chromosome contains a few thousand genes, that "code for" all cellular proteins.
Diploid: indicates that our body cells have 23 pairs of chromosomes - and every time our body cells reproduce, each NEW cell must also end up with 23 pairs of chromosomes. We will discus this today.
Haploid: indicates that a cell has only ONE copy of each chromosome - this is necessary for the process of sexual reproduction. A human egg is haploid (has 23 chromosomes) and a sperm is haploid (has 23 chromosomes). Upon fertilization, the new baby now has the 'correct' human number of 46 chromosomes in each of its somatic cells. We will talk about this Wednesday.
III. Mitosis: how 1 cell divides into 2 identical cells
Cells do not just divide randomly into two cells
during cell division; they must also distribute an exact copy
of each of their chromosomes to each new cell.
Why the need to be so precise? Each chromosome contains thousands of genes, each necessary to the proper functioning of the organism. It is vital that each new cell gets the same set of chromosomes that its parent cell once had!
Humans have ~30,000 genes spread over 46 chromosomes in EACH ONE of our somatic (body) cells. EACH ONE of these cells is genetically indentical to each other.
Obviously, some SERIOUS organizational skills are needed to make sure this process runs smoothly......
A cell first prepares to go through mitosis by first making a copy of its all of its DNA (DNA replication; in S phase), so that each new cell can receive a complete set of chromosomes.
After S phase, each replicated chromosome is then composed of two identical parts - each copy of DNA is called a sister chromatid, held together by a centromere. The chromatids need to stay together to keep things "organized" in the cell.
Overview: Before DNA Replication (S Phase) - one chromosome
After DNA Replication (but before mitosis) - a duplicated chromosome, made up of 2 sister chromatids
VI. DNA replication - a closer look
DNA before replication: 1 double helix
Every time one of our cells divides, our DNA first has to be replicated - copied. In fact, 3 billion bases have to be copied precisely in 4-6 hours!!!! How does this event occur??
DNA after replication: 2 identical double helixes
The DNA double helix is perfectly suited for replication because each strand can serve as a template (mold) to produce a shape opposite to itself.
A cast of enzymes and proteins accomplish DNA replication:
1. The two strands of DNA are "unzipped" (bonds broken between bases) by the unwinding enzyme DNA helicase
2. New nucleotides are inserted by complementary base pairing (A to T, C to G etc) by the enzyme DNA polymerase
3. New nucleotides are linked together at their sugar-phosphate groups by the enzyme DNA ligase, forming a new double helix from one strand of "old" and one strand of "new" DNA. Because the DNA molecule contains one new strand and one old strand, the replication process is termed semi-conservative (Fig 6-5; don't need to know the details).
4. DNA repair enzymes "proofread" and correct mistakes
5. DNA is organized on a protein "scaffold": Each chromosome is one giant molecule of DNA millions of base pairs long. If stretched out, this would equal ~1 yard of DNA per cell! Histone proteins bind tightly to DNA and keep the chromosomes wound up tightly around "spools" of histones called nucleosomes.
6. After DNA replication, 2 complete DNA molecules are present, identical to each other and to the original DNA molecule
V. Stages of Mitosis: How 1 cell becomes 2
The overall process: The sister
chromatids are pulled apart during mitosis (division of
the nucleus), and partitioned into the 2 new daughter cells by cytokinesis
(division of the cell). And all in 5 convenient steps! Note:
these steps are 'artificial' in that mitosis is a continuous
process, it does not 'stop' at these stages, but proceeds
smoothly through. However, it is convenient for us to
think of it in steps!
| Prophase: Chromosomes condense |
| Prometaphase: Chromosomes attach to spindle |
| Metaphase: Chromosomes align |
| Anaphase: Chromosomes separate |
| Telophase: Chromosomes relax |
| The end result of mitosis = 2 daughter cells, genetically identical to the parent cell. |
Mitosis Movies: Animation, another animation, OK, another animation, and a real cell !
VI. Cancer cells escape the controls on cell division:
1. What is cancer? Cancer is essentially a disease of mitosis - the normal 'checkpoints' regularing mitosis are ignored or overriden by the cancer cell. Cancer begins when a single cell is transformed, or converted from a normal cell to a cancer cell.
Often this is because of a change in function or a DNA mutation that occurs in one of several genes that normally function to control growth. Examples:
(1) the p53 gene, the "guardian of the genome", usually functions to properly control the cell cycle. However, p53 is mutated in over 50% of all human cancers.
(2) the BRCA 1 gene, the "Breast Cancer Gene" normally functions to supress tumor formation; but if a gene contains mutations such that BRCA1 does not work properly, tumor formation can begin (Note: mutations in this gene do not mean that a person will develop breast cancer, just that they have an increased risk for breast cancer).Once these crucial Cell Cycle genes start behaving abnormally, cancer cells start to proliferate wildly by repeated, uncontrolled mitosis.
2. Tumors - Good Cells gone Bad...? The cancer cells proliferate to form mass of cancer cells called a tumor. As the tumor grows larger, it begins to release proteins from the cell to attract new blood vessel growth (this is called angiogenesis). At point the tumor contains ~ 1 million cells and is about the size of a 'bb'.Benign: tumor cells remain at original site. Can be removed surgically or killed by radiation, usually eliminating any further cancer development at that site.
Malignant: some tumor cells send out signals that tell the body to produce a new blood vessel at the tumor site. These cells not only have their own food and oxygen supply, they also have an avenue for escape to a new part of the body - through the new blood vessel and into bloodstream. Cells that break away from the tumor begin to spread to surrounding tissues (via the bloodstream or lymph) and start new tumors = metastasis. Usually surgery is performed to remove the tumor, followed by radiation and chemotherapy.
So, why do chemotherapy drugs cause a person's hair to fall out? See this week's WarmUp!
3. Unusual features of Cancer Cells.(1) Cancer cells are frequently "immortal": whereas normal cells divide about 50 times and them die, cancer cells can go on dividing indefinitely if supplied with nutrients (A common laboratory cell line, HeLa cells, was originally isolated from a tumor in 1951 and is still growing).
(2) Cancer cells often have unusual numbers of chromosomes or mutations in chromosomes. Aging (production of toxic oxygen "free radicals"), exposure to toxins (like components of tobacco tar), mutagens (like ultraviolet light) all cause mutations in genes and cancer; but normal errors in DNA replication can lead transformation of the cell if they occur in a crucial gene.
(3) Cancer cells may also have an abnormal cell surface; instead of "sticking" to its neighboring cells, cancer calls tend to "round up" and break attachments its neighbors cells, allowing for metastasis.
(4) Cancer cells ignore the usual density-dependent inhibition of growth in cell culture (or in body tissues), multiplying after contact with other cells are made, piling up until all nutrients are exhausted.
Objectives: After this lecture, your should be able to:
