Cell Biology/Cell division/Mitosis

Mitosis is the normal type of cell division. Before the cells can divide, the chromosomes will have duplicated and the cell will have twice the normal set of genes.

The first step of cell division is prophase, during which the nucleus dissolves and the chromosomes begin migration to the midline of the cell. (Some biology textbooks insert a phase called "prometaphase" at this point.)The second step, known as metaphase, occurs when all the chromosomes are aligned in pairs along the midline of the cell. As the cell enters anaphase, the chromatids, which form the chromosomes, will separate and drift toward opposite poles of the cell. As the separated chromatids, now termed chromosomes, reach the poles, the cell will enter telophase and nuclei will start to reform. The process of mitosis ends after the nuclei have reformed and the cell membrane begins to separate the cell into two daughter cells, during cytokinesis.

The mitotic phase which includes both mitosis and cytokinesis is the shortest part of the cell cycle. The interphase cycle accounts for about 90% of the cell cycle. This phase is where the cell grows and copies its chromosomes in preparation for cell division. In the G1 phase which is also called the “first gap” the cell grows as it copies its chromosomes. In S phase, the cell starts to synthesize the DNA and completes preparation for cell division. In G2 it starts to divide.

In biology, Mitosis is the process of chromosome segregation and nuclear division that follows replication of the genetic material in eukaryotic cells. This process assures that each daughter nucleus receives a complete copy of the organism's genetic material. In most eukaryotes, mitosis is accompanied with cell division or cytokinesis, but there are many exceptions, for instance among fungi. There is another process called meiosis, in which the daughter nuclei receive half the chromosomes of the parent, which is involved in gamete formation and other similar processes, which makes the parent cell still active.

Mitosis is divided into several stages, with the remainder of the cell's growth cycle considered interphase. Properly speaking, a typical cell cycle involves a series of stages: G1, the first growth phase; S, where the genetic material is duplicated; G2, the second growth phase; and M, where the nucleus divides through mitosis. Mitosis is divided into prophase, prometaphase, metaphase, anaphase and telophase.

The whole procedure is very similar among most eukaryotes, with only minor variations. As prokaryotes lack a nucleus and only have a single chromosome with no centromere, they cannot be properly said to undergo mitosis.

Prophase


The genetic material (DNA), which normally exists in the form of chromatin condenses into a highly ordered structure called a chromosome. Since the genetic material has been duplicated, there are two identical copies of each chromosome in the cell. Identical chromosomes (called sister chromosomes) are attached to each other at a DNA element present on every chromosome called the centromere. When chromosomes are paired up and attached, each individual chromosome in the pair is called a chromatid, while the whole unit (confusingly) is called a chromosome. Just to be even more confusing, when the chromatids separate, they are no longer called chromatids, but are called chromosomes again. The task of mitosis is to assure that one copy of each sister chromatid - and only one copy - goes to each daughter cell after cell division.

The other important piece of hardware in mitosis is the centriole, which serves as a sort of anchor. During prophase, the two centrioles - which replicate independently of mitosis - begin recruiting microtubules (which may be thought of as cellular ropes or poles) and forming a mitotic spindle between them. By increasing the length of the spindle (growing the microtubules), the centrioles push apart to opposite ends of the cell nucleus. It should be noted that many eukaryotes, for instance plants, lack centrioles although the basic process is still similar.

Prometaphase
Some biology texts do not include this phase, considering it a part of prophase. In this phase, the nuclear membrane dissolves in some eukaryotes, reforming later once mitosis is complete. This is called open mitosis, found in most multicellular forms. Many protists undergo closed mitosis, in which the nuclear membrane persists throughout.

Now kinetochores begin to form at the centromeres. This is a complex structure that may be thought of as an 'eyelet' for the microtubule 'rope' - it is the attaching point by which chromosomes may be secured. The kinetochore is an enormously complex structure that is not yet fully understood. Two kinetochores form on each chromosome - one for each chromatid.

When the spindle grows to sufficient length, the microtubules begin searching for kinetochores to attach to.

Metaphase
As microtubules find and attach to kinetochores, they begin to line up in the middle of the cell. Proper segragation requires that every kinetochore be attached to a microtubule before separation begins. It is thought that unattached kinetochores control this process by generating a signal - the mitotic spindle checkpoint - that tells the cell to wait before proceeding to anaphase. There are many theories as to how this is accomplished, some of them involving the generation of tension when both microtubules are attached to the kinetochore.

When chromosomes are bivalently attached - when both kinetochores are attached to microtubules emanating from each centriole - they line up in the middle of the spindle, forming what is called the metaphase plate. This does not occur in every organism - in some cases chromosomes move back and forth between the centrioles randomly, only roughly lining up along the midline.

Anaphase


Anaphase is the stage of meiosis or mitosis when chromosomes separate and move to opposite poles of the cell (opposite ends of the nuclear spindle). Centromeres are broken and chromatids rip apart.

When every kinetochore is attached to a microtubule and the chromosomes have lined up along the middle of the spindle, the cell proceeds to anaphase. This is divided into two phases. First, the proteins that bind the sister chromatids together are cloven, allowing them to separate. They are pulled apart by the microtubules, towards the respective centrioles to which they are attached. Next, the spindle axis elongates, driving the centrioles (and the set of chromosomes to which they are attached) apart to opposite ends of the cell. These two stages are sometimes called 'early' and 'late' anaphase.

At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.

Telophase


The nonkinetochore microtubules elongate the cell and try to cut the cell in two. The nuclear envelopes start to become created by fragments of the parents cell’s nuclear envelope. Then, the chromatids start to become less tightly coiled together. By this point, cytokinesis is fully under way.

Cytokinesis
Cytokinesis refers to the physical division of one eukaryotic cell. Cytokinesis generally follows the replication of the cell's chromosomes, usually mitotically, but sometimes meiotically. Except for some special cases, the amount of cytoplasm in each daughter cell is the same. In animal cells, the cell membrane forms a cleavage furrow and pinches apart like a balloon. In plant cells, a cell plate forms, which becomes the new cell wall separating the daughters. Various patterns occur in other groups.

In plant cells, cytokinesis is followed through by the usage of contracting ring of microfilaments that pull the cleavage furrow within itself, cutting the cell in two. In plant cells, vesicles from the Golgi apparatus start to form a cell plate within the center of the cell. When this cell plate solidifies and connects the two ends of the cell, a new cell wall is created and two daughter cells are produced.



Regulation of Cell Cycle
Protein kinases are enzymes that activate or inactivate other proteins by phosphorylating them. These give out the signals for the G1 and G2 checkpoints to occur. However, to be active, the kinase must be attached to a cyclin. This is why it is called a CDK or a cyclin-dependent kinase.

Internal kinetochores exhibit a wait function. Not until all kinetochores are attached to a spindle microtubule does the cell process starts. This helps prevent some chromosomes from being left behind. Density dependent inhibition is when cells have a cue to multiply until a certain level of density is fulfilled. This means that a cell keeps multiplying until there is a full layer or until a certain level of pressure is built upon each other.

One possible explanation of why cancer cells do not follow normal signals is because they have an abnormality in the signaling pathway that conveys the growth factor’s signal to the cell-cycle control system. Usually, a cell will follow normal checkpoints due to the release of CDK in the system that regulate the cell process. However, in a cancer cell, the checkpoints are random. This means that because the cell does not follow density-dependent inhibition or follow the growth signals, the cell replicates at random points.