After we speak about reminiscences in biology, we are likely to concentrate on the mind and the storage of data in neurons. However there are many different reminiscences that persist inside our cells. Cells bear in mind their developmental historical past, whether or not they’ve been uncovered to pathogens, and so forth. And that raises a query that has been difficult to reply: How does one thing as basic as a cell maintain on to info throughout a number of divisions?
There is not any one reply, and the small print are actually tough to work out in lots of instances. However scientists have now labored out one reminiscence system intimately. Cells are capable of bear in mind when their mum or dad had a tough time dividing—an issue that is usually related to DNA harm and most cancers. And, if the issues are substantial sufficient, the 2 cells that end result from a division will cease dividing themselves.
Setting a timer
In multicellular organisms, cell division may be very rigorously regulated. Uncontrolled division is the hallmark of cancers. However issues with the person segments of division—issues like copying DNA, repairing any harm, ensuring every daughter cell will get the fitting variety of chromosomes—can result in mutations. So, the cell division course of contains numerous checkpoints the place the cell makes positive all the pieces has labored correctly.
But when a cell makes it by all of the checkpoints, it is presumably all good, proper? Not totally, because it seems.
Mitosis is the portion of cell division the place the duplicated chromosomes get separated out to every of the daughter cells. Spending plenty of time in mitosis can imply that the chromosomes have picked up harm, which can trigger issues sooner or later. And prior analysis discovered that some cells derived from the retina will register when mitosis takes too lengthy, and the daughter cells will cease dividing.
The brand new work, finished by a workforce of researchers in Okinawa, Japan, and San Diego, began by exhibiting that this habits wasn’t restricted to retinal cells—it appears to be a normal response to a sluggish mitosis. Cautious timing experiments confirmed that the longer cells spent attempting to endure mitosis, the extra possible the daughter cells can be to cease dividing. The researchers time period this method a “mitotic stopwatch.”
So, how does a cell function a stopwatch? It is not like it could ask Siri to set a timer—it is largely caught working with nucleic acids and proteins.
It seems that, like many issues relayed to cell division, the reply comes all the way down to a protein named p53. It is a protein that is key to many pathways that detect harm to cells and cease them from dividing if there are issues. (Chances are you’ll recollect it from our current protection of the event of elephant stem cells.)
A stopwatch manufactured from proteins
The researchers discovered that, whereas mitosis was happening, p53 began exhibiting up in a fancy with two different proteins (ubiquitin-specific protease 28 and the creatively named p53-binding protein 1). If you happen to made mutations in one of many proteins that blocked this advanced from forming, the mitotic stopwatch stopped ticking. This three-protein advanced solely began constructing as much as important ranges if mitosis took longer than traditional, and it remained steady as soon as it shaped in order that it might get handed on to the daughter cells as soon as cell division was accomplished.
So, why does this advanced kind solely when mitosis takes longer than traditional? The important thing turned out to be a protein known as a kinase, which attaches a phosphate to different proteins. The researchers screened chemical substances that inhibit particular kinases which might be lively throughout mitosis and DNA restore, and located a selected one which was wanted for the mitotic stopwatch. Within the absence of this kinase (PLK1, for the curious), the three-protein advanced does not kind.
So, the researchers suppose that the stopwatch seems to be like this: throughout mitosis, the kinase slowly attaches a phosphate to one of many proteins, permitting it to kind the three-protein advanced. If mitosis will get finished shortly sufficient, the degrees of this advanced do not get very excessive, and it has no impact on the cell. But when mitosis goes extra shortly, then the advanced begins increase, and it is steady sufficient that it is nonetheless round in each daughter cells. The existence of the advanced helps stabilize the p53 protein, permitting it to cease future cell divisions as soon as it is current at excessive sufficient ranges.
In keeping with this concept, all three of the proteins within the advanced are tumor suppressors, which means that mutations in them make tumor formation extra possible. The researchers confirmed that the mitotic stopwatch was regularly faulty in tumor samples.
So, that is how particular person cells handle to retailer one in all their reminiscences—the reminiscence of issues with cell division. The mitotic stopwatch, nevertheless, is simply one of many reminiscence storage programs, with fully separate programs dealing with completely different reminiscences. And, on the identical time that is occurring, a lot of different pathways additionally feed into the exercise of p53. So, whereas the mitotic stopwatch might effectively deal with one particular sort of downside, it is built-in into plenty of extra, advanced programs working within the cell.
Science, 2024. DOI: 10.1126/science.add9528 (About DOIs).
