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Course: Biology library > Unit 15
Lesson 4: Cell cycle regulation, cancer, and stem cellsCell cycle checkpoints
Google ClassroomHow cells use checkpoints at the end of G1 phase, end of G2 phase, and partway through M phase (the spindle checkpoint) to regulate the cell cycle.
Introduction
As cells move through the cell cycle, do they breeze through from one phase to the next? If they're cancer cells, the answer might be yes. Normal cells, however, move through the cell cycle in a regulated way. They use information about their own internal state and cues from the environment around them to decide whether to proceed with cell division. This regulation makes sure that cells don't divide under unfavorable conditions (for instance, when their DNA is damaged, or when there isn't room for more cells in a tissue or organ).
Cell cycle checkpoints
A checkpoint is a stage in the eukaryotic cell cycle at which the cell examines internal and external cues and "decides" whether or not to move forward with division.
There are a number of checkpoints, but the three most important ones are:
- The G
- The G
- The spindle checkpoint, at the transition from metaphase to anaphase.
The G
The G
At the G
- Size. Is the cell large enough to divide?
- Nutrients. Does the cell have enough energy reserves or available nutrients to divide?
- Molecular signals. Is the cell receiving positive cues (such as growth factors) from neighbors?
- DNA integrity. Is any of the DNA damaged?
These are not the only factors that can affect progression through the G
If a cell doesn’t get the go-ahead cues it needs at the G
The G
To make sure that cell division goes smoothly (produces healthy daughter cells with complete, undamaged DNA), the cell has an additional checkpoint before M phase, called the G
- DNA integrity. Is any of the DNA damaged?
- DNA replication. Was the DNA completely copied during S phase?
If errors or damage are detected, the cell will pause at the G
If the damage is irreparable, the cell may undergo apoptosis, or programmed cell death
The spindle checkpoint
The M checkpoint is also known as the spindle checkpoint: here, the cell examines 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 all the chromosomes are firmly attached to at least two spindle fibers from opposite poles of the cell.
How does this checkpoint work? It seems that cells don't actually scan the metaphase plate to confirm that all of the chromosomes are there. Instead, they look for "straggler" chromosomes that are in the wrong place (e.g., floating around in the cytoplasm)
How do the checkpoints actually work?
This article gives a high-level overview of cell cycle control, outlining the factors that influence a cell’s decision to pause or progress at each checkpoint. However, you may be wondering what these factors actually do to the cell, or change inside of it, to cause (or block) progression from one phase of the cell cycle to the next.
The general answer is that internal and external cues trigger signaling pathways inside the cell that activate, or inactivate, a set of core proteins that move the cell cycle forward. You can learn more about these proteins, and see examples of how they are affected by cues such as DNA damage, in the article on cell cycle regulators.
Want to join the conversation?
If cells who have broken DNA automatically die, then would it be possible for a chemical to be given to cancer patients, that would break or make the infected cells think their DNA was broken? Wouldn't this kill out the cancer?(13 votes)
There are many repair processes for DNA breaks — for KhanAcademy material on this see:
https://www.khanacademy.org/tag/dna-repair
Consequently, it is unlikely for a single break to kill a cell.
That being said, radiation treatment and (most?) chemotherapy drugs do exactly what you are suggesting — they cause large amounts of DNA damage and overwhelm the ability of rapidly dividing cells§ to repair themselves.
This usually leads to cell death.
§This includes the cancer cells we want to kill, but also many healthy cells including those renewing the lining of the gut and in hair follicles. Killing of healthy cells is a big part of why people undergoing cancer treatment often feel very ill and lose their hair.(31 votes)
Do the same checkpoints exist in meiosis? Thank you!(10 votes)- Good question!
Yes, recent research has shown that regulation of meiosis is similar to that of mitosis (though somewhat more complicated).
References and further reading:
https://www.sciencedirect.com/science/article/pii/S153458070800172X
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411289/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080918/
http://rstb.royalsocietypublishing.org/content/365/1546/1653(12 votes)
what happens to a cell if it does not “pass” the spindle checkpoint?(7 votes)
In this case, the cell would not continue past metaphase, rather wait until the spindle fibers have all attached to the sister chromatids. If the fibers have still missed some chromatids, then either the cell will divide incorrectly with unequal genetic material in the daughter cells or it will have the proper checks in place to initiate cell death.(12 votes)
why would damage to a cell's DNA prevent it from doing it's job?(4 votes)- The DNA is sort of like the instructions for building, operating, and maintaining a cell. If those instructions get damaged then things start to go wrong.
Maybe this analogy will help?
Imagine you were trying to build a model by following written instructions. Part way through you discover that something has damaged a section of the instructions. You do your best, but at the end your project ends up being a bit messed up.
Then someone makes a photocopy of your damaged directions, which end up even less clear than your original. They then try to build another copy of the model, which ends up even more flawed than your version ...
Does any of that help?(16 votes)
- what happens if cells don't divide(2 votes)
- It will kill itself if it can't fix itself. Cell suicide is called apoptosis.(6 votes)
- How many strategies are there to increase the activity of checkpoints? I think it will be a great hypothesis for anticancer drug design.(4 votes)
Quite interesting!
I found an article explaining the therapeutic potential and short backs of that approach. It turns out that targeting cell checkpoints may be a double-edge sword for cancer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037895/
DNA- and mitotic spindle-damaging drugs are even mainstream in cancer therapy. While there is no something to 'increase' activity, there are things which target and damage points.
Actually, drugs are inhibitors for checkpoints so it automatically leads to apoptosis.
The drawback is that these inhibitors don't work in all types of tumors.(6 votes)
If there are checkpoints, then why are there still people with extra/missing chromosomes because the spindles do not attach/do their job (e.g. down syndrome)?(2 votes)
Alright well the most common form of down syndrome is known as trisomy 21, which is when a person has 47 chromosomes instead of 46 chromosomes in each cell. This is caused by nondisjunction, which gives a gamete an extra copy of chromosome 21. Nondisjunction would occur at the spindle checkpoint, and so the cell is supposed to be stopped and the error corrected there. However, if the spindle checkpoint isn't working properly, nondisjunction can occur and the cell will go on with the division even with that error present, resulting in conditions such as trisomy 23.(9 votes)
- In the second paragraph it mentions that there are on cell cycle checkpoints in eukaryotic cells. Does this mean that bacteria don't have cell cycle checkpoints?(4 votes)
I don't want to say that they don't have any checkpoints, but they don't have these clear checkpoints like eukaryotic cells. In eukaryotic cells there are clear phases of the cell cycle, where for example the genetic material must be duplicated (in Synthesis phase) before the cell can divide (during mitosis). In bacteria, these different phases of the cell cycle can overlap. For example when E. coli is dividing really fast because there are lots of nutrients around, it can already start copying its DNA for the next division cycle whilst it has still not divided into two cells in this round.
There is also some variation among bacteria, but even if there are not these checkpoints like the eukaryotic ones, they are still sensing and responding to things that are going on with their DNA. For example there is the 'SOS response' which can prevent certain cell cycle processes in response to DNA damage. There seems to be some disagreement about calling this a checkpoint though.(4 votes)
- Does anyone know what goes on at the cellular level that prevents scar tissue from healing? Thank you.(5 votes)
- For each of the three main checkpoints in the cell cycle, indicates what could happen if the checkpoint didn't function?(4 votes)
