After we discuss recollections in biology, we are likely to give attention to the mind and the storage of data in neurons. However there are many different recollections that persist inside our cells. Cells keep 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 elementary as a cell maintain on to info throughout a number of divisions?
There isn’t any one reply, and the main points are actually tough to work out in lots of instances. However scientists have now labored out one reminiscence system intimately. Cells are capable of keep in mind when their dad or mum had a tough time dividing—an issue that is typically related to DNA harm and most cancers. And, if the issues are substantial sufficient, the 2 cells that outcome from a division will cease dividing themselves.
Setting a timer
In multicellular organisms, cell division could be very fastidiously 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 suitable variety of chromosomes—can result in mutations. So, the cell division course of consists of numerous checkpoints the place the cell makes positive all the pieces has labored correctly.
But when a cell makes it by means of all of the checkpoints, it is presumably all good, proper? Not fully, 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 a variety 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, carried out by a group of researchers in Okinawa, Japan, and San Diego, began by exhibiting that this conduct wasn’t restricted to retinal cells—it appears to be a normal response to a gradual mitosis. Cautious timing experiments confirmed that the longer cells spent attempting to bear mitosis, the extra possible the daughter cells could be to cease dividing. The researchers time period this technique a “mitotic stopwatch.”
So, how does a cell function a stopwatch? It isn’t like it may well 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 right 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. (It’s possible you’ll recollect it from our latest protection of the event of elephant stem cells.)
A stopwatch product of proteins
The researchers discovered that, whereas mitosis was occurring, p53 began exhibiting up in a posh with two different proteins (ubiquitin-specific protease 28 and the creatively named p53-binding protein 1). When you 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 regular, and it remained steady as soon as it fashioned in order that it could 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 regular? The important thing turned out to be a protein referred to as a kinase, which attaches a phosphate to different proteins. The researchers screened chemical compounds that inhibit particular kinases which are energetic 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 appears 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 carried out 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 slowly, then the advanced begins build up, 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 step 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 ceaselessly faulty in tumor samples.
So, that is how particular person cells handle to retailer considered one of their recollections—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 totally different recollections. And, on the similar time that is taking place, numerous different pathways additionally feed into the exercise of p53. So, whereas the mitotic stopwatch could effectively deal with one particular sort of drawback, it is built-in into a variety of extra, advanced programs working within the cell.
Science, 2024. DOI: 10.1126/science.add9528 (About DOIs).
