In the cellular machine shop

Justin Courcelle Studies cellular replication, its mechanisms, processes, and rules.

Human cell

It's chapter one, page one of Biology 101, cells are the basic unit of life. From the smallest microorganism to the largest plants and animals, cells make everything. Cells convert energy to grow and adapt to their environment. Perhaps most important to life on Earth is that cells can reproduce and pass the genetic information encoded in their DNA to the next generation.

How cells reproduce and pass along their genetic information is the research focus of cancer biologist Dr. Justin Courcelle. While the field of cellular reproduction is by no means uncharted territory, it has only been within the last few decades that the tools available to scientists have become sophisticated enough for the curious to unlock the doors of these small rooms and look at their inner workings. Essential to the cell's ability to reproduce itself is the capacity of the DNA molecule to replicate accurately.

According to Dr. Courcelle, the cellular mechanisms that perform the task of replicating DNA work well. If they didn't, diseases that originate at the cellular level, like cancer, for instance, would be far more prevalent.

Diseases like cancer occur when cells make mistakes when reproducing the genomic language. One reason errors occur is an altered genetic code. If the genetic instructions change, the cell may no longer organize and regulate itself, allowing cells to grow when and where they shouldn't.

"The reality is," Dr. Courcelle said, "DNA is a remarkably active molecule. Sunlight damages DNA; just breathing oxygen causes damage to DNA. So cells have to have a way to recognize the damage and repair it when the replication machinery encounters it."

In a paper, "Fate of the replisome following arrest by UV-induced DNA damage in Escherichia coli," published in the Proceedings of the National Academy of Sciences' Early Edition, Dr. Courcelle details findings of a recent study conducted in their lab that illuminates the mechanisms and processes by which cells repair damaged DNA in E. coli.

In DNA reproduction, the cellular machinery responsible for duplicating the DNA is called the replisome. In undamaged DNA, the replisome unwinds and splits the double-helix allowing for the synthesis of two identical new strands. Researchers know little about what happens to the replisome when this process took place on damaged strands of DNA, the kind of DNA that can lead to changes in genetic information and cancer if not repaired.

Dr. Courcelle's paper depicts the strange and magnificent workings of cellular biology in living E. coli cells. Lesions caused by ultra-violet irradiation on strands of DNA block the replisome, stopping it from unwinding the DNA. Dr. Courcelle's findings report that in this circumstance, parts of the replisome can disengage from the rest of the machine in a way that allows repair enzymes to get in and fix the damaged strand. When the damaged strand is repaired, the replisome gets back to work. It's the depiction of a molecular machine shop where the cell is a mechanic with the right tools to repair the machines when damaged to keep everything running.

"The information that we see now is telling us that the cell is trying to avoid skipping over or breaking down when it hits the damaged areas. It's a fix-it-as-you-go strategy," Dr. Courcelle said.

While Dr. Courcelle's experiments were performed using E. coli (the use of E. coli as a subject for genetic research is widespread) DNA damaged by UV radiation, similar proteins associated with the process are found replisomes of human DNA as well.

"The cellular processes in E. coli might not be the same as in humans," Dr. Courcelle said, "but they're certainly doing something similar."

Courcelle noted the link between the processes of DNA replication, aging, and, of course, cancer. While everyone ages, not everyone gets cancer. According to the American Cancer Society's 2012 Cancer Facts & Figures report, an estimated 1,638,910 Americans had cancer in 2012; that's .005% of the total population. Statistics like these are a testament to the cell's extraordinary ability to repair damaged strands of DNA.

"In the long run," Courcelle said, "for cancer research, we hope that science will be able to identify particular proteins that are responsible for making the mistakes in certain situations. With that knowledge, people may avoid certain chemicals and conditions that trick cells into making mistakes. On the other hand, if we could increase the cell's ability to repair damaged DNA just twofold in the grand scheme of things, we might be able to push back the age when people usually get cancer, so instead of getting lung cancer when you're 60, you would get it when you're 120. In terms of this kind of preventative care, there's a lot of hope that we can improve on those processes, or at least identify how to make them work better in the human body."