Your body's cells adapt to stress to avoid making mistakes

Your body's cells adapt to stress to avoid making mistakes

Our biological building blocks may be much more resilient than scientists thought possible

Produced in partnership with MiSciWriters.

On the surface, our lives seem like they are divided into hard, discrete stages defined by age. When you turn 13, you don’t need a guardian to watch the PG-13 movies. When you are 18, you are no longer a minor.

But sometimes events can happen earlier or later than “normal.” I was 10 when my family moved to the United States, and I was placed a grade below where I should have been age-wise thanks to my lack of language skills. It took a couple years for my English to catch up to the recommended reading level that matched with my age.

Cells, the basic building block of living things, also have different life stages, and scientists have long thought that this cycle doesn't vary. But like the life forms they make up, it's not quite that simple. In a recent study, researchers found that they could manipulate the cells' environment to blur the boundaries between the different stages. This has implications for helping unravel diseases, such as cancer, whose cells often act abnormally, which has made it harder for scientists to find cures for them.

A cell needs to undergo certain events to fully prepare itself for division, which is how cell populations regenerate. First, the cell cranks up its biological processes, like making proteins, and it grows in size. Then the cell copies its DNA – the hereditary material that serves as a blueprint for all of the cell’s biological processes – to ensure that the resulting two daughter cells have identical and equal amounts. Finally, the cell divides during a process called mitosis. Then the two daughter cells repeat the cycle again.

As long as scientists have known about cell division, it's been conventional wisdom that its stages only occur in one unimpeachable order: grow, copy DNA, and divide. But sometimes, things don't go quite as expected. One possible result of things going awry is for cells to show what scientists call common fragile sites (CFSs), or gaps and breaks in chromosomes, the structures in each cell that package DNA.

CFSs form when DNA replication is slowed or halted, called replication stress. It can be caused by a myriad of chemicals and environmental factors and can have severe health consequences. One example is folate deficiency, a condition characterized by low levels of folate or folic acid. If a pregnant woman is folate deficient, it can be deadly to the child, causing preterm delivery, low birth weight, or slowed growth.

Stained human cells. Blue parts are DNA.

Gerry Shaw

In the laboratory, there is a compound called aphidicolin that is commonly used to induce artificial replication stress in cells. Ian Hickson’s team at the University of Copenhagen used it in a series of experiments to induce replication stress and see whether DNA gets copied at CFSs after other parts of the chromosomes have been replicated already. To observe the effects of the aphidicolin, researchers used a technology called immunofluorescence, which allows them to visualize the presence or absence of a target protein under a microscope. If there is a fluorescent signal, your target is present.

In this way, the researchers were able to visualize both the presence of active DNA replication and a protein that is known to localize near CFSs. Together, the researchers were able to see if DNA replication was occurring at CFSs in cells. The researchers looked at two different conditions – grown with aphidicolin and without.

The team found that in cells grown with aphidicolin, CFSs actually continue to replicate in mitosis. On the other hand, the cells grown without aphidicolin did not show this replication, so it's not an event that happens under a normal condition. That is, when replication is artificially slowed down, the cells adapted, continuing the replication process for longer than scientists thought possible. These findings go against the idea of having hard, discrete boundaries of the cell cycle.

Why do CFSs act this way when under replication stress? Are the cells trying to ensure that its entire DNA is replicated, even if it means finishing the job a later time than usual? Perhaps this is a situation similar to how I had to work hard to catch up to my peers’ level of English – it's a necessary task because, if unaddressed, the consequences might be detrimental.

Unlike me learning English, it is difficult to imagine that a cell is consciously making a decision to replicate CFSs during mitosis to alleviate the damages caused by aphidicolin. But maybe it is nature’s way of telling us, yet again, that life is resilient, and it can adapt to more than we realize.

Any questions?

Ask Irene Park