Hi. In this video, we're going to talk about G1 phase and S phase entry. So, we're at the very beginning of the cell cycle here. G1 phase is a growth phase that occurs after interphase but before DNA replication and cell division. This is the phase where the cell is just growing. It's getting ready to divide. It's helping create all these things that it's going to need to divide into 2 cells. So, it's just growing a lot. And this is a really important time for cell cycle regulation because once the cell says, "Okay, I'm leaving G1 phase and entering the S phase," it has got to commit to that. Because once it gets to the S phase, the cell has to divide or die. So, if G1 phase hasn't done its job and the cell enters S phase, it's either going to be too small to divide or it's not going to be able to divide and it's going to die, and that's just a waste of a cell. Right. So, this transition here is regulated by the start checkpoint. So, just important to know that start you know, is this checkpoint super important and is crucial in this G1 to S phase.
Now, what stimulates the cell to grow? These are things called mitogens, and mitogens are just these extracellular signals that can be hormones, they can be chemicals, they can be proteins, just these extracellular signals that the cell receives usually during interphase that say, "Okay, I'm getting ready to divide, so we need to start growing." And so, mitogens, usually when they interact with the cell, they stimulate some kind of downstream pathway that will activate the cyclins and cyclin-dependent kinases for the G1 phase. But they also inhibit things like S and M phase cyclins right, because sometimes the cells have just divided and very fast-growing cells, or sometimes there might be residual of these left over. But the cell is like, "Okay, I need to grow before I go into S phase or M phase." So if there's any of these lying around either from a previous cell division or just low levels of expression, these mitogens come in and inhibit them so that the cell has time to grow before the cell can divide. So this is kind of an example of this, you don't need to know any of these particular names, but what you see is there's some type of mitogen signal here, and they come in and they activate cyclins, their cyclin-dependent kinases, various transcription factors, other cyclins, that come in and they act at very different places in the cell cycle. The G1-S checkpoint, the G2-M checkpoint, all of these things, are activated by these mitogens that come in and stimulate the cell cycle. But like I said, you don't need to know this pathway, just sort of know the conceptual image of it.
So that's all good. Right? Because the cell is growing, but the cell has lived its life. Right? It's getting ready to divide, it's maybe an old cell, and so there's probably some damage to it. And one of the things that it can have is DNA damage. If the DNA is damaged then the cell is like, "Okay, I've got to repair this." So, when the G1 phase is gonna halt. And so, when it stops in the G1 phase, this gives time for this protein called p53, to sense that DNA damage. So what is p53 is going to be a transcription regulator, and it acts to halt entrance into S phase if the DNA is damaged. Now, you can imagine if this is such a crucial important protein to recognize DNA damage and stop the cell cycle, you can imagine that this is a really important target for cancers. And, p53 is actually mutated in a huge amount of cancers. Because you can think if p53 isn't doing its job, then the cell is going to divide even if it has DNA damage. And a lot of mean most if not all cancers are based on DNA damage. So, when p53 is active, it's sort of halting this. But if there's some other reason or p53 or any of these factors kind of get stimulated and the cell decides, "You know, I'm not ready for division because I have some serious problems. Either I'm not big enough, my DNA is damaged, I have some stresses around me and I just don't feel comfortable dividing." Then it enters this phase called G0, and this is a non-dividing state. So the cell can remain here pretty much like indefinitely, it usually doesn't, it usually will come out a bit eventually, but it can. And it will sort of repair itself in whatever way it needs to before it enters G1. Now cells that don't divide, things like nerve cells, they actually enter into G0 and then they stay there forever because they're not dividing so they don't need to be going through all these different phases.
Here's an example of p53 in the cell cycle. So, here you have some type of DNA damage that the cell has recognized, It then can activate p53. And p53 will halt the cell cycle, promote DNA repair, and stimulate the cell cycle restart, if the DNA can be repaired. But if it can't, it actually can go ahead and stimulate apoptosis, which is remember, cell death, and sort of eliminate the cell. But essentially, p53 is super important in maintaining the stability of the DNA and making sure there are no errors. So it's a super super super important protein, and a big field in cancer research is actually studying mutated forms of p53 and how it acts to cause cancer. So now, let's move on.
