Cell Cycle:
A typical eukaryotic cell contains DNA that forms a number of distinct chromosomes. Human somatic (body) cells have 46 chromosomes. When human cells divide, each cell inherits a copy of each of the 46 chromosomes. The organelles must also be apportioned in the appropriate numbers. This process occurs in the cell cycle.
Let's review the following terms: somatic cells, gametes, genome, chromosome, chromatid, and centromere (kinetochore).
Somatic Cells: Regular body cells.
Gametes: Cells that you form specifically for reproduction: sperm and egg.
Genome: A cell’s total DNA allotment. A human’s genome is contained in 46 chromosomes.
Chromosome: A gene is made up of DNA, which codes for one or more polypeptides. A
chromosome is made up of many genes. The DNA in the chromosome is wrapped around histone and non-histone proteins. Before DNA synthesis, there is only one double stranded helix of DNA in each chromosome.
Chromatid: After DNA synthesis, there are two identical DNA helices connected by a structure called the centromere. Each DNA helix is called a chromatid. After DNA synthesis, the chromosome is made up of two identical chromatids connected by a centromere (region)
(kinetochore: actual structure). The centromeres act as handles. These chromatids are called sister chromatids.
The cell cycle is an endless repetition of mitosis, cytokinesis, growth, and chromosomal replication. Some cells, for example, fingernail cells, break out of the cycle to die, thus performing their
function.
Stages of the cycle:
Traditionally, the cell cycle has been divided into 4 stages: G1 phase, S phase, G2 phase, and M
phase.
M = mitosis, S = synthesis of DNA and histones, G1 and G2 = gap 1 and gap 2.
G1 Phase or the Gap 1 Phase: The chromosomes decondense as they enter the G1 phase; this is a
physiologically active time for the cell. The cell synthesizes the necessary enzymes and proteins needed for cell growth. DNA consists of a single unreplicated helix (with histone and non-histone proteins). In the G1, the cell may be growing, active, and performing many intense biochemical
activities.
S Phase or the Synthesis Phase: DNA and chromosomal proteins are replicated. This phase lasts a few hours.
G2 Phase or the Gap 2 Phase: Between synthesis and mitosis. The mitotic spindle proteins are
during mitosis.)
M phase: Mitosis and Cytokinesis. Mitosis is the division of the nucleus, which is usually followed by cytokinesis (division of the cytoplasm).
Regulation of the cell cycle:
Different types of cells take different amounts of time to complete the cell cycle. For example, bean cells take 19 hours to complete the cycle: 7 hours in the S phase, 5 hours in the G1 and G2 phase, and
2 hours in mitosis.
Some cells, for example, nerve cells, do not go through the cell cycle and no longer divide.
If cells divide too rapidly, they invade specialized tissues. This disrupts the function of the tissue and is referred to as cancer.
The Condensed Chromosomes:
The chromosomes begin to condense after the S phase of the cell cycle. These chromosomes can be seen under the light microscope. Each chromosome consists of two copies of the same chromatid. Each chromatid is joined together by a constricted area common to both chromatids. This region of attachment is known as the centromere. Within the constricted region is a disc shaped protein containing structure-- the kinetochore. This is where the microtubules of the spindle are attached.
Mitosis and Cell Division:
Mitosis: duplication and division of the nucleus and the chromosomes contained there in, usually followed by cytokinesis..
The Gap 1, Synthesis, and Gap 2 stages have been described as Interphase. The M stage (mitosis) has five phases: Prophase, Prometaphase, Metaphase, Anaphase, and Telophase. The letters IPPMAT describe the cell cycle. Gap 1, Synthesis and Gap 2 phases are all parts of Interphase.
Interphase occurs first and prepares the cell for mitosis. During interphase, the cell grows, replicates the DNA and chromosomal proteins, and grows.
Stages of Mitosis: Prophase:
1) Chromosomes condense; histone I and RNA molecules play an important role in the supercoiling of the chromosomes. The chromosomes get more compact and become visible. What we draw as chromosomes are the chromosomes after they condense.
2) Nucleoli disappear. The nucleolus is made up of different parts of different chromosomes. When the chromosomes condense, the chromosomal parts are pulled out of the nucleolus, and the nucleolus disappears.
Prometaphase:
1) Nuclear envelope fragments
2) Microtubules of the spindle can now invade the nucleus and interact with the chromosomes. 3) Spindle fibers extend from the poles to the equator.
The spindle: the spindle apparatus which moves the chromosomes consists of two proteins: actin and tubulin. At the beginning of mitosis, the two centrosomes (centrioles in animal cells) that were fairly close together move to the opposite poles of the nucleus. As the nuclear membrane
disappears, the spindle forms between the two centrosomes. During interphase, the centrosome duplicates to form two centrosomes just outside of the nucleus.
The spindle apparatus is composed of three different types of spindle fibers:
1) Kinetochore spindle fibers: These attach from the kinetochore of the chromosome to the centrosome.
2) Polar spindle fibers: These attach one centrosome to the other centrosome. 3) Aster spindle fibers: These attach the centrosome to the cell membrane.
When spindle microtubules are formed, the microtubules of the cytoskeleton are partially disassembled. The microtubules are formed from tubulin (protein) dimers, which are borrowed from the cytoskeleton. After cell division the spindle is taken apart, and the cytoskeleton network is put back together.
The spindle microtubules elongate by incorporating more subunits of the protein tubulin. Several parallel microtubules form spindle fibers. The assembly of spindle microtubules is started in the centrosome, microtubule organizing center. Microtubules are polar with distinct ends-- a '+' and '-' end. The + ends are moving away from the centrosome. The microtubule changes length by the addition or removal of proteins at the + end.
If the cells contain centrioles, a pair of newly formed centrioles marks each pole. The cells with centrioles have a third set of spindle fibers called the ASTER. These may brace the poles against the cell membrane during the movements of mitosis. The rigid cell wall of plant cells may perform a similar function.
Centrioles and the Microtubule Organizing Center:
It was once thought that the centriole had a large part in the formation of the cell's spindle.
However, cells that do not have centrioles form the spindle. Cells without centrioles, when stained, show a dark region where the microtubules originate (Centrosome). This region seems to be where the microtubules originate. It has been suggested that the spindle separates the centrioles and basal bodies to ensure that the cells can construct flagella and cilia.
However, as soon as the microtubule from the other pole attaches to the kinetochore, it pulls the chromosome toward the other pole aligning the chromosomes at the equatorial plane. Microtubules can only remain attached to a kinetochore when there is a force exerted on the chromosome from the opposite end of the cell. ).
There are three types of nonkinetochore microtubules:
1) Some microtubules radiate from the centrosome towards the metaphase plate without attaching to chromosomes. Others are too short to reach the metaphase plate.
2) Still others extend across the plate and overlap with nonkinetochore microtubules from the opposite pole of the cell.
3) Aster fibers: these extend from the centrosome to the cell membrane. Along with the polar spindle fibers, these are thought to anchor the centrosome in one place.
Metaphase:
The chromosomes line up on a plane called the metaphase plate. This lies in the middle of the spindle apparatus and is perpendicular to its axis. In actuality, the centromere/kinetochore is the only thing that lines up on the plate, the chromatids on the chromosomes can be pointing in any direction.
At metaphase, the chromosomes are aligned on the cell's midline. Approximately 15-35 microtubules are attached to the kinetochore (by kinetochore microtubules
Anaphase:
Anaphase begins when an enzyme breaks down the protein that holds the sister chromatids together and the spindle apparatus starts pulling the kinetochores to the opposite poles (kinetochore
microtubules shorten as chromosomes approach the poles). The daughter kinetochores move apart dragging the chromosomes (each now a single strand) to the poles. Two cells begin to form.
Microtubules pull a chromosome towards a pole by losing protein subunits at their centrosome and at the + end (attached to the kinetochore). How this works is unknown. The nonkinetochore microtubules are responsible for elongating the whole cell along the polar axis during anaphase.
Telophase: Reverse of prophase, but there are now two nuclei instead of one. 1) Chromosomes decondense
2) Nuclear membrane reappears. 3) Spindle fibers become disorganized.
4) The cell pinches in the middle, beginning the formation of two cells.
Cytokinesis: Division of the cytoplasm. Cytokinesis in Animal Cells:
Cytokinesis usually begins with a cleavage furrow at the metaphase plate by an indentation in the surface of the cell. It looks as though the cell membrane were being pulled toward the middle, as if a thread were being wrapped around the cell and being tightened.
actin microfibrils that are found in the cytoplasm just beneath the cell membrane. The furrow deepens until the cell is pinched in two.
Cytokinesis in Plant Cells:
At the time of telophase, small membranous vesicles filled with polysaccharides; formed in the Golgi complex, form on the metaphase plate. The vesicles continue to form until they are more or less continuous and form a double membrane, which is called the cell plate. The cell plate becomes impregnated with pectin and forms a cell wall. The cell plate forms across the midline of the plant cell where the old metaphase plate was located.
What can control the cell cycle?
1) Certain chemicals are present in the cytoplasm. These will drive the cell cycle.
2) The Cell-Cycle Control System directs the sequential events of a cell cycle. This system is a set of molecules that coordinates key events in the cell cycle. This acts as a built in clock. 3) It is important that cells divide only upon reaching a certain size. Cells need to be large
enough to ensure that the daughter cells will contain the necessary machinery to survive. 4) A number of environmental factors such as depletion of nutrients, changes in temperature
and pH can stop a cell from growing and dividing. Cells require growth factors at various stages of the cell cycle. For example: Platelet-derived growth factor (PDGF) is important in wound healing. This factor increases cell division at the site of a wound.
5) Internal Message: When the kinetochores are all attached with the KSF this activates Anaphase promoting complex (APC). The APC breaks down the protein that holds the sister chromatids together.
6) The density of cells can control cell division. Cells need space to divide as crowding inhibits cell division. This is called DENSITY-DEPENDENT INHIBITION. Related to density-dependent inhibition (anchorage dependence) is a requirement for the adhesion of cells to a substructure. Cells will stop dividing if they lose anchorage. Cancer cells do not exhibit density-dependent inhibition.
When normal cells stop growing due to changes in the environment or when touching other cells, they stop growing during the G1 phase of the cell cycle. This point is known as the R (restriction)
point. Once a cell passes through the R point, the cell is committed to the M phase. If the cell doesn't divide, it enters the G0 phase or the nondividing state. The R point acts as a ‘check point.’
For most dividing cells passing through the R point, cell size seems to be the crucial factor. A cell must grow to a certain size in the G1 phase for DNA synthesis to occur.
There are two types of proteins that regulate and drive the cell cycle: protein kinases and proteolytic enzymes.
1) Protein Kinases: These proteins activate and inactivate molecules by phosphorylating them. Specific protein kinases move molecules through the G1 and G2 checkpoints. Most of the time the kinases are inactive. They are activated when the kinases attach to the protein cyclin. They are called cyclin dependent kinases (cdk).
the cell from late G2 (interphase) to mitosis. The level of MPF increases and decreases-- MPF
appears in late interphase and reaches the highest concentration during mitosis. MPF disappears after mitosis.
MPF acts as a protein kinase and leads to the phosphorylation of certain chromatin proteins that cause the chromosomes to condense during prophase. MPF also stimulates the proteins in the nuclear lamina and other kinases, which fragments the nuclear envelope.
2) Proteolytic Enzymes: These enzymes break down proteins. Proteolytic enzymes controls the onset of anaphase by breaking down the protein that holds the sister chromatids together. They also breakdown cyclin thus deactivating the kinases.
A final look at mitosis and cell division:
Cell division consists of mitosis (nuclear and chromosomal events) and cytokinesis (cell membrane and cytoplasm events). Mitotic cell division serves organisms in 2 ways:
1) Single cell organisms: Mitosis allow for an increase in the population. This is a form of asexual reproduction. There is no exchange of genes between individuals. The colony will be made up of individuals with genes that are identical to the founder. These are called clones. This is called Binary Fission.
2) Multicellular Organisms:
a) Mitosis and cytokinesis allow an organism to grow in size while maintaining the surface area/volume ratio of its cells.
b) Mitosis and cytokinesis allow for specialization of cell types through cell differentiation. c) Mitosis and cytokinesis that are dead or damaged allow cells to be replaced.
Abnormal Cell Division: Cancer Cells.
Cancer cells do not respond to normal cell division controls. They divide excessively and ignore density-dependent inhibition.
Cancer cells, if they stop growing, also seem to stop at random points in the cell cycle and not at the restriction point. Cancer cells can go on dividing indefinitely. Most mammalian cells will divide about 20-50 times before many stop, age and die. However, there is a line of laboratory maintained cancer cells called HeLa cells that have been dividing since 1951. HeLa is from Henrieta Lachs, an African American female who died in 1951. Her cancer cells still survive and are now world-wide. In fact, all of the cells together are 400 times Henrietta’s body weight. Her cells have excellent telomeres.
The first step in cancer cell formation is transformation, which is the conversion of a normal cell to a cancer cell. Usually the immune system destroys such cells. However, sometimes the cell can evade destruction. It will divide to form a tumor (a mass of cells in normal tissue). If the cells remain at the original site, it is a benign tumor. Malignant tumors spread.
form attachments to neighboring cells and extracellular substructure. This process allows cancer to spread.
