Mitosis and Meiosis

Centrioles are only found in animal cells. Nerve and muscle cells do not divide. Some cells, such as the liver, exist in the G0 state but can move into mitosis if called upon. In G2, organelles, membranes, and proteins needed for mitosis are duplicated.

Interphase

The nucleus is well-defined, and DNA is loosely packed into long chromatin fibers. DNA cannot be read since it is in its chromatin form. DNA is negatively charged, and the double helix is wrapped around positively-charged histone proteins. This fiber of wrapped DNA is called chromatin. When these fibers are condensed further, that form is called chromosomes. DNA condenses because loose chromatin could be tangled. The typical chromosome is called a duplicated chromosome, with 2 sister chromatids attached at the centromere. Single-strands of DNA are also considered chromosomes, just not the duplicated kind.

Prophase

Chromatin condenses into visible chromosomes. Centrioles move to the opposite poles of the cell. The nucleolus and nuclear membrane break down/disappear. Protein fibers cross the cell to form the mitotic spindle (microtubules). This is the longest phase.

Prometaphase

Spindle fibers attach to the centromeres. Spindle fibers can be split into two groups- kinetochore and nonkinetochore microtubules. Kinetochore microtubules attach to the kinetochore in the centromere to eventually pull the sister chromatids apart. Nonkinetochore microtubules span the length of the cell and eventually help to elongate it. The chromosomes begin moving to the center of the cell.

Metaphase

Chromosomes align along the center of the cell, known as the metaphase plate. The spindle fibers coordinate this movement and help to make sure the chromatids are split correctly. This is the shortest phase.

Anaphase

The sister chromatids begin to separate at the kinetochores. They are moved by actin and myosin, which are proteins that ‘walk’ along the spindle fibers as they are phosphorylated, causing a conformational shape change. The end of the spindle fiber dismantles into tubulin as the walking occurs. The proteins in the centromere must first be inactivated, so the chromatids can be pulled apart into their individual chromosomes. The nonkinetochore microtubules lengthen to elongate the cell.

Telophase

The chromosomes arrive at the opposite poles. Daughter nuclei and nucleoli form. Chromosomes and spindle fibers disperse. Chromosomes are no longer visible as they unwind into chromatin. Cytokinesis begins.

Cytokinesis

In animal cells, the constriction belt of actin filaments form a cleavage furrow, pinching the cell in two. In plant cells, the golgi body produces vesicles that line up along the center of the cell. The cellulose-filled vesicles fuse to form the cell plate, which will eventually become the cell wall.

Mitotic Index

The mitotic index shows what proportion of a tissue is in mitosis. An index of 0 indicates that no cells are in mitosis, while an index of 1 indicates that all cells are in mitosis. The formula is (the number of cells in mitosis)/(total number of cells). Aka - (P+M+A+T)/(I+P+M+A+T). This is used to diagnose cancer - high MI indicates that tissue is more likely to be cancerous. Additionally, after cancer treatment, MI is measured to see if the index has gone down.

Evolution of Mitosis

Mitosis evolved from binary fission in prokaryotes. This is how prokaryotes reproduce. In binary fission, DNA is duplicated and cytoplasm is split, because there are no membrane-bound organelles. As organisms got more complex, their mechanisms got more complex.

Regulation of Cell Division

The cell cycle is controlled by ‘stop’ and ‘go’ signals. These signals indicate if cellular processes have been successfully carried out. Chemical signals (proteins) in the cytoplasm give cue. Internal signals are called promoting factors, while external signals are called growth factors. Most often, a kinase enzyme (cause phosphorylation) activates or inactivates cell signals. Cyclins are regulatory proteins that have cyclical levels through the cell cycle. CDKs, or cyclin-dependent kinases, undergo a shape change as cyclin attaches to them, either activating or inactivating a protein. These are always present in the cell. These regulatory proteins are highly conserved. MPF, or maturation promoting factor, is the complex formed when a cyclin and CDK combine.

G1- can and should DNA synthesis begin? Is replicated necessary? Does the cell have enough nutrients and is it big enough? This is the most critical checkpoint. If the cell receives a ‘stop’ signal, it exits the cycle and switches to the G0 phase.

G2 - Was DNA replicated correctly? Is the cell large enough? If the cell receives a ‘stop’ signal, it undergoes apoptosis.

M/spindle - Are the spindle fibers attached correctly? If the cell receives a ‘stop’ signal, it undergoes apoptosis.

Growth Factors

These are a form of communication between neighboring cells. They tell other cells when to divide. One example of this is density-dependent inhibition. Crowded cells stop dividing, as no to overcrowd. Each cell receives some growth factor, but at a certain high density, not one cell has enough growth factor to divide. Another example is anchorage dependence. Cells can only grow on a certain substrate or medium. For example, liver cells can’t grow on the pancreas. This keeps cells in the right place.

Growth Factors and Cancer

Proto-oncogenes - they are typically off, and they activate cell division. They are only turned on when cells need to divide. If they are switched on for an extended period of time, they can cause cancer. One example is RAS, which activates cyclins.

Tumor-suppressor genes - they are typically on, and they inhibit cell division. They are only turned off when cells need to divide. If they are switched off for an extended period of time, they can cause cancer. One example is p53.

Cancer

Cancer is a failure of cell division control. Checkpoint stops are lost. Gene p53 halts cell division in G1 if damaged DNA is detected. It causes apoptosis. All cancers shut down this gene’s ability to function. A cell must experience 6 key mutations to become cancerous:

• unlimited growth (turn on growth promoter genes)
• ignore checkpoints (turn off tumor-suppressor genes (p53))
• escape apoptosis (turn off suicide genes)
• become immortal for unlimited divisions (turn on chromosome maintenance genes)
• promote blood vessel growth (turn on blood vessel growth genes)
• overcome anchor and density dependence (turn off touch-suppressor genes)

Mutations can be caused by UV radiation, chemical exposure, radiation exposure, heat, smoke, pollution, age and genetics.

Benign means that the abnormal cells have remained at the original site, while malignant means that the cells have migrated, and are impairing body functions.

Treatments include high-energy radiation, which kill rapidly-dividing cells, or chemotherapy, which stops DNA replication, mitosis, cytokinesis, and blood vessel growth.

Meiosis

Although meiosis is a reduction-division, chromosomes are still doubled because it is an add-on from mitosis, which evolved first. The mechanism worked well enough, so it was conserved. This process is also known as gametogenesis, or the formation of gametes. Meiosis starts with a germ cell - an oocyte in females and a spermatocyte in males. These cells are diploid, containing 23 single-stranded chromosomes from mom and 23 single-stranded chromosomes from dad. Gametes are haploid, meaning that they contain 23 single-stranded chromosomes.

Prophase 1

Chromatin condenses into chromosomes and the nucleus and nucleolus break down and disappear. Since DNA has already been copied, there are now 23 duplicated chromosomes from mom and 23 duplicated chromosomes from dad. During synapsis, these duplicated chromosomes find their homologous pair from the other parent and form a tetrad. These then share DNA in a process called crossing over. The point at which they cross over is called the chiasmata. This leads to genetic variation, increasing the survival likelihood of a species.

Metaphase 1

The maternal and paternal chromosomes randomly align at the equator of the cell due to independent assortment. This is another source of genetic variation, as maternal or paternal chromosomes could be pulled to either future daughter cell.

Anaphase 1

Homologous chromosomes separate, but centromeres and sister chromatids are still together.

Telophase 1

This results in 2 haploid cells, since the homologous pairs are in different cells. This is also accomplished by an actin filament or cell plate. These cells do not go into interphase, but straight into meiosis 2.

Prophase 2

Centrioles move to the poles, and the spindle fibers are produced. The nucleus and nucleolus have already disappeared.

Metaphase 2

The chromosomes line up at the equator and spindle fibers attach to the centromere

Anaphase 2

Sister chromatids separate and move to the poles of the cell

Telophase 2

The nucleus and nucleolus reform, and chromatids uncoil into chromatin. 4 haploid cells with 23 chromosomes are produced. In females, one egg cell is produced along with 3 polar bodies, which die. In males, 4 sperm cells are produced.