To understand and appreciate the importance of the role of this family of genes, a foundation of knowledge of the cell life cycle is essential. The cell cycle is what allows the organs and tissues of your body to work in perfect harmony, enabling growth and repair to maintain balance throughout the fabric of your body. At the most simple level it is divided into three main stages: interphase, a long period of cell activity and preparation for division; mitosis, the precursor to the split of the mother cell into two identical daughter cells; and cytokinesis, the breathtaking moment when the cytoplasm pinches off into its two distinct successors to continue the ever-ebbing flow of cellular life. This entire process takes on average 24 hours - as the sun rises and sets around us, as do our cells.
During interphase, many critical tasks are undertaken alongside the cell's particular function in anticipation of a successful future division. The first step of the interphase is known as G1 - the first growth - and plays the role of increasing the space within the cell to maximise its capacity for division, while upregulating the synthesis of proteins that aid organelle production. This stage relies on a perfect balance of free nucleotides, amino acids, temperature and nutrients to provide the right conditions to engender life. The DNA only commences replication during the following S (synthesis) stage to form two sister chromatids for every homologous chromosome pair, provided that materials and space are sufficient for this to be carried out effectively. The final stage of interphase is G2 (the second growth) in which organelles are replicated to be distributed between the two daughter cells using the materials collected during the first growth. Energy stores are also increased to enable the motor proteins to carry out the processes on the spindle fibers in the following mitosis phase, which is typically an active process. Finally, DNA is checked for errors before initiating the mitotic division.
Mitosis in eukaryotes - a group of nucleus-containing organisms to which humans belong - involves four main stages. The first is the prophase, during which the chromatin genetic material condenses within the nucleus into chromosomes, which literally means 'colour bodies' since these more compact forms of DNA are clearly visible when using staining techniques such as giemsa staining, or when viewing material on a spectral karyotype. The centrosomes organise themselves to either pole of the cell where they form the tubulin spindle which will later play a pivotal role during the mitotic phase. Finally, the nucleoli break down, which ends the production of ribosomes. By metaphase, the kinetochores have attached to the centromeres on the chromatids and the spindle joins onto the centre of these kinetochores for the purpose of pulling the chromatids towards the equator of the cell. In anaphase A, the centromeres split and the microtubule spindles depolymerise and shorten, causing them to retract and pull each chromosome from the pair of sister chromatids to either pole of the cell. This is followed by anaphase B, involving the movement of the centrosomes closer to the cell membrane to ensure that segregation is easy. The final stage of mitosis is telophase, which finishes off the last of the spindles by full depolymerisation. A nuclear envelope is assembled surrounding the genetic material located on each side of the cell.
The last part of the cell cycle involved in its renewal for further cell activity and growth is cytokinesis, which causes the cell membrane to pinch the cytoplasm into two separate, yet identical, daughter cells, each containing their own full set of genetic information. Since plants have a cell wall, this stage instead involves the formation of a cell plate through the middle of the cytoplasm, which eventually segregates into the product cells.
With a process so complex and laced with so many fine yet vital details, it is unsurprising that there is the potential for errors to occur. Common faults in this system are marked by product cells with the wrong amount of genetic material (aneuploid cells) or with damaged DNA. If sister chromatids fail to separate during anaphase, one daughter will have monosomy as it loses material while the other has too much and experiences trisomy. Binucleated cells also have the potential to occur if during cytokinesis, the cell fails to divide the nuclei evenly between the two product cells. However, the error most commonly tied to cancer occurs as the cell divides too effectively and loses control of its own mechanisms, propelling it into a state of frenzied division and propagation, and planting faulty gene-containing seeds throughout the tissues. This erroneous division is known as a tumour and is often benign, yet can be secretly perfidious if it metastasises and is carried as a vector of malfunction throughout the bloodstream to germinate elsewhere. There are many theories as to how cancer arises, and there is no direct answer. The sparks that ignite this disease vary not only between cancer types, but also from individual to individual, which is what sets it apart from other conditions in its unique difficulty to be studied. A common hypothesis that marries genetic causes with environmental factors is known as the 'two-hit' theory, which suggests that heritable mutations may be passed on in one copy of a tumour suppressor gene. This means that - despite this inheritance - the other copy of the gene is still present to encode the cell-regulating protein and thus the single mutation at first has no effect. This is often coupled with genomic instability, meaning that - in a twisted draw of probability - it is highly likely that environmental factors cause a second hit which eliminates the other copy of the gene and prevents the cell-controlling protein from being synthesised at all, thus resulting in the breakdown of any barriers to incessant replication.
Fortunately, your cells are equipped with reinforced mechanisms to prevent the spread of damaged DNA, in the form of many regular checkpoints throughout the normal cell cycle.
The first of these is known as the restriction point and occurs between the G1 and S phases of the cycle. This confirms that cell conditions are optimal for the cell cycle to proceed, including having the right balance of nutrients and extracellular conditions. Until this point, the cell cycle has relied upon external growth factors to move forwards; following the restriction point, the cell becomes committed to the cycle and no longer requires growth factors, but is also unable to leave the process. If the cell fails at restriction point, the cell cycle is terminated and the cell is instead sent into the G0 phase. This is not a mechanism solely used for errors detected - for example, neurones are fully differentiated and therefore do not need to remain in the cell cycle. Other potential causes for G0 initiation include a lack of nutrients. The G0 phase may be quiescent, allowing it to be reversed, or irreversible such as during senescence and terminal differentiation. Senescence is a way to allow cells to continue their typical function until they die, without further divisions. If a grave mistake in the DNA or irreparable structural damage is present, the cell may undergo a more brutal process of apoptosis, eradicating the cell and physically preventing it from differentiating or carry out erroneous functions which may lead to cancer. Evidently, mutations which cause loopholes in the restriction point may allow damaged cells to slip past these regulations and commence cancerous divisions.
The second checkpoint of the cell cycle is the G2 point which ensures that there are no further damages to the DNA before mitosis is initiated, and gives cells the opportunity to repair and re-synthesise any faulty sections of DNA.
Another checkpoint is present during the phase of mitosis itself, known as the spindle checkpoint since it occurs during metaphase, when the microtubule spindle is in use. It makes sure that each chromosome is properly connected tot he spindle by its kinetochore, thus confirming that division during the succeeding anaphase A will segregate chromatids properly and ensure that the daughter cells are truly diploidal and identical. Defects in this checkpoint, as with all other checkpoints, run the risk of cancer arising from aneuploids. Cancer is not the only impact triggered during this stage: Down syndrome is engendered by trisomy in the 21st chromosome if the chromatids are not split evenly across the two daughter cells during embryonic development.
Every day, your body's complex machinery creates around 330 billion cells each day, many of which are secret precursors to cancer. Thanks to the beautiful and carefully refined mechanisms that act within each cell's cycle, you are constantly halting the formation of tumours before they could even be noticed under a microscope. While these systems are not without their faults and occasional environmental and genetic factors have the potential to tip it into a precarious state of imbalance, it is still worth admiring our capacity to regain order, if not with the help of our ever-advancing oncological technology. It is important that we stop perceiving cancer in a single-faceted manner, as a simple fight between humanity and the human body. We are equipped with nature's all-encompassing user manual deep within our cells, and it is up to us to step up to the task of decoding it.
https://en.wikipedia.org/wiki/Mitosis#Further_reading
27.01.2024
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