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The Life Cycle of a Cell
The Life Cycle of a Cell
Cells are living things, of course, so it is appropriate that we refer to their lifespan and activities as a cell's life cycle. Cells involve many different signals, chemical reactions, and more depending on the cell's jobs, of course. But, there is a general life cycle that applies to most cells that are nice and general. That life cycle is shown here.
As you can see, the cell's life cycle is typically represented in a circle (because it is a cycle) that renews when the cell reproduces...but more on that later.
Let's focus for now on just the 2 major phases:
Interphase
Mitotic Phase
Interphase, as shown in grey in the outer circle, comprises the vast majority of the cell's life. The mitotic phase, shown in the peach color, makes up just a small sliver of time in a cell's life. Let's zoom in on each of these phases a bit more.
Interphase: The Vast Majority of a Cell's Life
Interphase: The Vast Majority of a Cell's Life
As mentioned previously, interphase is the phase of life in which cells spend the vast majority of their lives. If a cell is functioning normally and doing its job, it is almost certainly in interphase. The only time cells leave interphase is when they are reproducing. As you can see in the diagram, interphase is made up of 3 sub-phases: the G1, S, and G2 phases. In reality, there is an unusual fourth phase known as the G0 phase, but we get to ignore that phase for our course! Let's talk about each of these phases individually:
G1 Phase - All About Growth
G1 Phase - All About Growth
During the G1 phase, the cell will start duplicating its organelles and other cellular components. This is the start of the preparations for mitosis, or cell division. The cell is eventually (during the mitotic phase) going to split into two cells, so it is going to have to grow larger and start to duplicate some important enzymes and other cellular components.
S Phase - All About Synthesis
S Phase - All About Synthesis
Just like in the previous phase, this phase will ultimately help to prepare for cell division as well. This time, however, the cell will duplicate its DNA - copying every chromosome so that there are copies of each to go into each daughter cell. The S standards for 'synthesis' because the cell is synthesizing, or building, new copies of DNA.
G2 Phase - Better Double-Check!
G2 Phase - Better Double-Check!
During this phase, the cell will be growing larger...again... and doubling more cellular components such as organelles. Now that the cell has doubled everything... hopefully... so you might be thinking that it is time to divide into two cells. Well, not quite. For reasons that will become apparent when we discuss mitosis in more depth, it is VERY important that cells be absolutely sure that everything is in order before they divide. Otherwise, some very serious issues will arise. So, this phase also includes checking to make sure that everything doubled properly before moving on to the mitotic phase of the cell cycle. In reality, some more growth of the cell occurs here too, but don't worry too much about that for this course.
Checkpoints Between These Phases
Checkpoints Between These Phases
These phases are all, in reality, separated by different 'checkpoints', or times in which the cell will check to make sure everything is in order before proceeding to the next phase. These checkpoints are crucial and were mentioned at the end of the G2 phase, but you do not need to memorize specifically what occurs in any checkpoint.
The G1 Checkpoint
The G1 checkpoint determines whether all conditions are favorable for cell division to proceed. The G1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. External influences, such as growth factors, play a large role in carrying the cell past the G1 checkpoint. In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G1 checkpoint. A cell that does not meet all the requirements will not be allowed to progress into the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G0 and await further signals when conditions improve.
The G2 Checkpoint
The G2 checkpoint bars entry into the mitotic phase if certain conditions are not met. As at the G1 checkpoint, cell size and protein reserves are assessed. However, the most important role of the G2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repairs the damaged DNA.
The M Checkpoint
The M checkpoint occurs near the end of the metaphase stage of karyokinesis. The M checkpoint is also known as the spindle checkpoint,, because it determines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell.
G0 Stage
Not all cells are continually replicating – some cells may enter into a non-dividing G0 stage. These cells may either be dormant (quiescent) or aging and deteriorating (senescent). Cells enter the G0 phase from the G1 phase; quiescent cells may re-enter G1 at a later time (senescent cells do not)
Normally, cells will only divide a finite time before reaching senescence (a typical human cell will divide ~ 40 - 60 times)Specialized cells will often permanently enter G0, as differentiation has prevented their capacity for further division
Neurons are examples of cells that have been arrested in a G0 state – these cells are amitotic (cannot divide)
External Controls of Cell Cycle
Anchorage Dependence and Density Dependent Inhibition
Cells anchor to the dish surface and divide (anchorage dependence).
When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition).
Nutrients & Growth Factors:
If essential nutrients are left out of the culture medium, cells will not divide.
Growth Factors- specific regulatory proteins released by certain body cells that stimulate other cells to divide (platelet-derived growth factor) bind to cell membrane receptors and stimulate cell division in fibroblasts (i.e. as a response to heal the wound
Signals and Internal Regulation and Controlling the Cell Cycle
Positive Regulation of the Cell Cycle
Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are termed, positive regulators. They are responsible for the progress of the cell through the various checkpoints. The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern. Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded by cytoplasmic enzymes.
Kinases are enzymes that activate other molecules (often other enzymes) by phosphorylating them (adding a phosphate to them)). Phosphorylation changes the 3-D shape of a molecule: if that change involves the active site of an enzyme, then we have a mechanism for turning enzyme activity on and off through allosteric regulation (where binding of a molecule at a binding site that’s away from an enzyme’s active site changes the active site).
Cyclin-dependent kinases, as you can tell by the name, are kinases whose activity depends on the concentration of cyclins. One of the first cyclin-dependent kinases to be studied was MPF, a molecule first discovered in frog eggs that promotes the entrance of cells into M phase from G2. MPF was originally studied in the context of frog development and stands for Maturation Promoting Factor. However, if you think of it as mitosis-promoting factor, it might assist you in remembering what this molecule does.
MPF is a molecular complex that consists of a cyclin that’s bound to a CDK (cyclin-dependent kinase). As you can see on the left, these two only combine to form MPF for a brief moment (during M phase).
The CDK level stays constant throughout the cell cycle. As we’ve seen, what fluctuates are the levels of cyclin. In the case of Cyclin B, its level rises from its lowest level during G1 and peaks during M. As cyclin levels rise, more and more cyclin binds with CDK, creating MPF. When MPF levels rise to their peak, the cell can pass the G2 checkpoint, allowing the cell to move into M phase, during which mitosis and cytokinesis occur.
During anaphase, cyclin (while still attached to MPF) is broken down. This renders MPF into its inactive form (CDK), and it will remain in that form until cyclin B again accumulates during the next cell cycle. Similar fluctuations in the levels of other cyclins are at work in controlling the move past the G1 checkpoint into S phase. At the M checkpoint, the cell “reads” levels of a protein complex that only forms when the spindle is attached to each and every chromosome at their kinetochores. This signal allows cells to proceed from metaphase to anaphase, moving towards the completion of mitosis.
Negative Regulaltion of Cell Cycle
The second group of cell-cycle regulatory molecules are negative regulators, which stop the cell cycle. Remember that in positive regulation, active molecules cause the cycle to progress.
The best understood negative regulatory molecules are retinoblastoma protein (Rb), p53, and p21. Retinoblastoma proteins are a group of tumor-suppressor proteins common in many cells.
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