Wednesday, 2 December 2020

Basics of Cell Cycle and Regulation

 Small molecules like hormones can act as messengers, interacting with receptors in the plasma membrane or or within the cell, that then amplify the signal or activate and carry out some cellular functions. As it happens, many of these signals regulate the cell cycle. This is the series of stages that a cell goes through in order to copy all of its genetic material and eventually divide into two daughter cells, which is how prokaryotic life initially proliferated billions of years ago.

This is also how new cells in our bodies form to replace the old ones. When cell division occurs, each new cell has a copy of all the genetic material, and these daughter cells are completely identical,

How do we get two cells from one?
  The first thing we have to do is understand how all the DNA is arranged in a cell. Each daughter cell needs a complete copy of all the genetic information, or genome, and while prokaryotes often have just one Circular DNA molecule, eukaryotic cells have many different linear DNA molecules, called chromosomes.

  All of this material has to undergo replication, and then the two sets must be separated before the cell divides, leaving each daughter cell with a copy. Different eukaryotic species have different numbers of chromosomes, and us humans have 46 chromosomes in all our somatic cells, which are basically all your cells, excluding the reproductive ones. That’s a set of 23 chromosomes from each parent.

  Each chromosome consists of a DNA molecule wrapped around proteins called histones to form nucleosomes. This chromatin fiber undergoes supercoiling for storage when not in use, but will uncoil to undergo replication. All the DNA in a chromosome is copied, resulting in two identical sister chromatids. These are attached at the center by a centromere, with the chromosomal arms extending on either side. Later, when the cell divides, the sister chromatids will separate and get pulled into each of the two daughter cells.

Although cells do divide, most of the time they are not dividing. They’re just being cells. The time that a cell spends dividing is called the M phase, or mitotic phase, and the time spent not dividing is called the interphase, or the phase in between divisions.

  The interphase is comprised of three subphases. Those are the G1 phase, or first Gap, the S phase, or Synthesis, when the genome gets copied, and the G2 phase, or second Gap. These gap phases were named as such because it first appeared that not much was happening during these times. Later we came to understand that there isan incredible amount of cellular activity that must occur in order to prepare for the S phase and the M phase. This is because the new cells don’t just need their own genome, they also need all of the other cellular components and organelles. so these must be produced as well.

The G1 phase, which marks the beginning of a cell’s life, involves cell growth. Some cells divide very infrequently, or not at all, so cells can spend a long time in this phase, or a related phase called G Zero. Other cells that divide more rapidly may spend only a few hours in this phase. In adult humans, the S phase takes ten to twelve hours, for two identical copies of the genome. The G2 phase takes about four to six hours, and involves more growth and preparation for cell division. And then the M phase, or mitosis, has the cell dividing into two daughter cells, which takes about an hour. Other animals have significantly different rates for these phases, as do human embryonic cells.

What controls the cell cycle? 

This is crucial to understand, because some cells inside the human body, like skin cells, are dividing very frequently, while liver cells don’t divide much at all, and fully formed nerve cells never do. These discrepancies can be accounted for when we examine the ways that the cell cycle is regulated on the molecular level. This is called the cell cycle control system, and it is regulated by small signalling molecules in the cytoplasm.

  These trigger and coordinate key events throughout the cycle. There are moments during or in between phases that are called checkpoints, where the cell must receive a specific signal to move forward. One of these occurs during the S phase, to ensure that DNA replication occurs without any problems, and others happen during he G1 phase, at the end of the G2 phase, and during the M phase.

So what could these signalling molecules be?
  Most of them are proteins that fall into two categories. Protein kinases, and cyclins.
The protein kinases are enzymes that activate or deactivate other proteins by phosphorylation, the act of adding a phosphate group to another molecule. This is one way that a message can be transmitted around a cell. These kinases are always in the cell, floating around, but they are usually inactive. Once attached to a cyclin, they become activated.
   Cyclins, unlike the kinases, have greatly varying concentrations in the cell, and a kinase that must be bound to a cyclin to activate is called a cyclin-dependent kinase. B-type, or mitotic cyclins are synthesized during the S and G2 phases, and once they coordinate with kinases, these MPF complexes,or maturation-promoting factors, allow the cycle to pass the G2 checkpoint, and then they perform a number of tasks throughout mitosis.

  Later in mitosis, cyclin gets degraded, and the kinases go back to being inactive until the next time around the cycle. There is also a checkpoint during the G1 phase that is called the restriction point. This is a stop point that must be overridden by a signal in order to continue to the rest of the cycle. In absence of this signal, the cell remains in the G1 phase or moves into the G Zero phase, which is a non dividing state.

Most of our cells are in the G Zero phase at at any given time, but these can be called back into the cell cycle by external signals like growth factors, which can be released during injury to stimulate cell growth to heal the wound. So we can think of the G1 checkpoint as the primary point point where the cell determines whether it will divide or not.
The third checkpoint is in the M phase, and it governs the separation of sister chromatids during mitosis.

  Regulation is incredibly important, because certain cells in your body need to divide rapidly and others shouldn’t divide at all. If cells are dividing they also need to know when to stop, like the way cells in a culture will stop dividing once they have filled up their container. This is called density-dependent inhibition. If the cells were to divide further, there would be no room, and they would all suffer.

  Alternately, if some are removed, they continue dividing again to fill up the vacancy. This occurs due to surface proteins on each cell. If they bind to receptors on adjacent cells, this sends a signal that inhibits cell division, even in the presence of growth factors, soonly the ones with empty space nearby continue to divide.

So what happens when regulation of the cell cycle goes wrong?
 
In a word, cancer. Cancer involves cells that are dividing out of control, which leads to the development of a tumor. Cancer cells are like regular cells, except that they do not follow the instructions carried by the signals that normally regulate the cell cycle. They may continue to divide even when no growth factor is present, or when there is no room for more cells. This can happen for many different reasons,which is why there are so many kinds of cancer, and they all stem from a genetic abnormality of one kind or another.

  A genetic mutation will alter the product of gene expression, and if this resulting protein is crucial for regulating the cell cycle, it can lead to what we call “transformation”, or behaving like a cancer cell. Sometimes if there are strange new proteins on the surface, this abnormal cell can be recognised by the immune system and destroyed ,but if not, it can divide rapidly and produce a tumor. This is why cancer treatment relies so heavily on understanding the science behind cell division and cell cycle regulation, as any cancer treatment that hopes to be even remotely effective absolutely must address the issue on this fundamental biological level. 

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