Sunday, February 5, 2017

Genetics (1/8): The cell cycle and mitosis

Genetics is the science that studies the hereditary characteristics of organisms and their transmission.


The key roles of cell division

Even after the completion of the development of the organism, cell division continues to have an important role because it serves to replace dead cells to aging or damaged cells.
Cell division involves the distribution of the same genetic material, the DNA, the two daughter cells.
The total genetic DNA of a cell constitutes the genome.
The eukaryotic genomes have a variable number of DNA molecules.
Before cell division, all of the DNA to be copied, and the 2 copies must be separated so that the 2 daughter cells possess a complete genome.
The DNA molecules are packaged within the chromosomes, and any eukaryotic species has a specific number of chromosomes inside the cell nucleus, in human somatic cells have 46 chromosomes, while in the reproductive cells (gametes), chromosomes are 23 .
In each chromosome is a DNA molecule that contains hundreds or thousands of genes.
The DNA is associated with proteins that maintain chromosome structure and help to control the activity of genes, and this organized along a thin filament association is called chromatin.
After that the cell has duplicated the DNA, the chromatin condenses and presents a narrowing of the area in the vicinity of a specialized call centromere area.
After each chromosome replication consists of two sister chromatids, which after the separation recede forming 2 complete sets of chromosomes in two new nuclei.
Mitosis is the division of the nucleus, which is usually followed by cytokinesis, the division of the cytoplasm.
After these sequences, by a cell are born 2 new cells.

While playing, the child inherits 46 chromosomes, 23 from each parent, which are combined in the nucleus of a single cell, when one father's sperm joins an egg of the mother cell to form a fertilized egg (zygote).
The reproduction of the gametes occurs through meiosis, which leads to the production of daughter cells which possess the half of the chromosomes of the parent cell.
Meiosis occurs only in the gonads (ovaries and testes).


The mitotic cell cycle

Mitosis is only part of the cell cycle.


Il ciclo cellulare mitotico

The mitotic phase or M phase includes mitosis and cytokinesis and is the shortest phase of the cell cycle.
Before it happens again mitosis there is a longer phase, the interphase, which occupies approximately 90% of the cycle.
During interphase the cell grows and copy their chromosomes in preparation for division.
The interphase can be divided into 3 sub-steps: first interval G1 phase, S phase and G2 phase (the second interval).
During the sub-phases, the cell grows by producing proteins and synthesizing organelles, while the chromosomes are duplicated only in S phase
A cell then grows in the G1 phase, continues to grow while copying the chromosomes in the S phase, completed his preparation for growth to the division in the G2 phase and is divided into M phase
Mitosis is then divided into 5 phases: prophase, prometaphase, metaphase, anaphase, telophase.

Many of the events of mitosis dependent on the mitotic spindle, a structure consisting of fibers of microtubule associated proteins.
The construction of the spindle microtubules begins at the centrosome, a non-membranous organelles, which requires the demolition of part of the microtubule cytoskeleton because there is enough material for its construction.
When you go into mitosis the two centrosomes are positioned near the nucleus, and move away during the prophase and prometaphase, producing the spindle microtubules.
Before the end of prometaphase the two centrosomes are at opposite poles of the cell and are called spindle poles.
Each of the two chromatids of a chromosome has a kinetochore, a structure made of protein and certain portions of DNA chromosomal centrometro.
During prometaphase kinetochores 1 of 2 is anchored by spindle microtubules, then the microtubules of opposite pole bind other kinetochore, making a kind of tug of war, ending in a draw, leaving the chromosome at the center.
In metaphase, the microtubules that do not stick overlap and the centrometri all duplicated chromosomes are on a plan called the metaphase plate, midway between the two poles.
During anaphase the chromosomes become chromatids are separated and move to opposite poles of the cell, at the end of this phase are located at opposite poles and the cell is stretched along its polar axis.
The nuclei are formed again during telophase, and then starts cytokinesis.
Cytokinesis occurs through the split, which begins with the appearance of a cleavage furrow, which starts to look like a little gap on the cell surface near the old metaphase plate, then the groove is deepened to strangle the mother cell and in 2 producing two completely separate daughters.
On the cytoplasmic side of the trench is a contractile ring of microfilaments consisting of actin and myosin, which contracting create the groove.

And 'likely that mitosis have originated in the most simple mechanisms of riprozione bacterial cell, in fact prokaryotes reproduce by binary fission, and most bacterial genes is contained in a single bacterial chromosome.


The cell cycle regulation

Different cell types have different frequencies of cell divisions, and for example, nerve cells and muscle cells of an adult man do not divide ever.

The sequence of cell cycle events is directed by a specific cell cycle control system, a set of cyclically active molecules within the cell, which triggers and coordinates the key events of the cycle.
This control system works independently, driven by a built orgologio, and is subjected to external and internal adjustment.

A point of a cell cycle control is a critical point through which the stop and start signals can pass through the loop.
These signals indicate that up to that point have been completed correctly cellular processes, and if it is necessary or not to restart the cell cycle.
The three main control points are located in the G1, G2, and M.
For many cells the most important point seems to be the G1, said restriction point.
If the cell does not receive a signal it exits the loop and enters a state where it does not split, called G0 phase (most of the human body is at this stage).

The regulating molecules are of type protein kinase, that is, enzymes that activate or inactivate other proteins through phosphorylation.
The kinase for activation must tie a cyclin, cyclin-dependent kinase forming (Cdk).
The of Cdk activity increases or decreases depending on the concentration of cyclin.
The MPF is a complex of cdk and is a factor that drives the cell to pass the G2 checkpoint to enter the M-phase, by acting both directly and indirectly, and after the M phase, the MPF is autodisattiva.
The enzyme portion of MPF, the Cdk, remains inactive until it binds with cyclin in a new cycle.
 

Internal signals
A signal that delays the anaphase originates from kinetochores who have not yet attached to the microtubule spindle, when certain proteins trigger a signaling pathway that maintains an inactive promotion dell'anafase complex (APC), and this waiting signal ceases only when all kinetochores are attached to the spindle.
The APC then becomes active and indirectly triggers the cyclin degradation and inactivation of proteins that hold sister chromatids together.
 

External signals
A growth factor is a protein released by cells, which stimulates the division of other cells.
The mammalian cells divide in culture only if the soil contains specific growth factors, and in general, each type of cell responds to certain growth factors or in combinations of them.
The density-dependent inhibition is a phenomenon which consists in stopping cell division due to crowding.
For example, if some cells are removed from the culture leaving a space, neighboring cells are duplicated until you fill that space.
The anchorage dependency is when to divide a cell must be anchored to a substrate, such as the inner surface of the culture vessel or the extracellular matrix of a tissue.

Cancer cells
Cancer cells are cells that divide excessively escaping the control of the organism, invading other tissues, if left unchecked can kill the whole organism.
In fact they ignore the normal signals that regulate the cell cycle, do not show contact inhibition and do not need of growth factors in the culture medium.
They can independently produce a certain growth factor and may present anomalies in the loop control system, ceasing to be divided into random points of the cycle.
Normal cells divide only 20 to 50 times before dying, as cancer cells, however, if continuously fed can divide indefinitely, they are immortal.
The cell transformation occurs when it is converted to normal in tumor cell that manages to escape the immune surveillance, which normally destroys foreign organisms.
The tumor is a mass of abnormal cells within a tissue for normal rest.
The benign tumor is when the abnormal cells remain in their original site, in which case that part can be removed surgically.
The malignant tumor is when abnormal cells spread in the body by damaging the functions of one or more organs.
Cancer is synonymous with malignancy.
These cells also may have an unusual number of chromosomes and their metabolism can be upset, and because of cell surface changes, lose contact with other similar cells and with the extracellular substrate, spreading to nearby tissues.
These cells can also be separated from the original tumor and enter the blood vessels, invading other parts of the body, causing other cancers, in a phenomenon called metastasis.
 

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