Part 1: What is DNA Damage?

I am proud to say that my paper describing some of my thesis research was published this week in the Early Edition of PNAS!

Getting my PhD in molecular biology didn’t happen overnight (more like a decade of college + grad school), so chances are if you aren’t a biologist yourself the paper might sound like gibberish written in a foreign language. So in an attempt to not bore you to death, I’m going to post a series of explainers on molecular biology ending with a summary of what I found. (Caution, that last post may contain traces of gibberish!)

I studied how DNA gets damaged, so let’s start with DNA. All of your genetic information, basically an instruction manual for how do build everything from the smallest parts of your cells to your entire body, is encoded into DNA molecules. That’s a lot of information, and if the DNA in just one of your cells was stretched out straight, it would be over 6 feet long! To pack all of that information into each microscopic cell in your body, the DNA molecules are tightly wound up and organized into structures called chromosomes. In order for organisms to grow and live, cells divide and their chromosomes are duplicated and segregated into the two new cells. In this way genetic information is passed down to the next generation, and the two new cells should be identical to the original cell.

However, this is not a perfect world. There are lots of ways that DNA can get damaged. Damage can be caused by things from outside the cell, like UV light which affects the structure of the DNA molecule. I’ll get into this in more detail, but DNA damage can ultimately lead to cancer, which is why a lot of sun exposure with all those UV rays can lead to skin cancer. In addition to UV, there are lots of chemicals, known as carcinogens, that can damage your DNA. But not all damage comes from outside the cell. Cells can accidentally damage their own DNA by doing things like making mistakes when duplicating their DNA or not segregating their chromosomes correctly during cell division.

If DNA damage does occur there are many negative outcomes. As I said, DNA encodes an instruction manual for your cells. If information is lost or mutated, the cell might not have everything it needs to live and it will die. That’s not such a big deal if the cell in question is one random skin cell on a human’s body, but if the cell is a single-celled organism like a bacterium or yeast, then that’s the end for that individual. In a less severe case, DNA mutations can lead to genetic diseases that don’t kill the cell or organism but change something about it. For example sickle cell anemia is a genetic disease in which a mutation in a single gene can cause a person’s red blood cells to be misshapen.

Another quite undesirable outcome of DNA damage is cancer. Each cell in your body is under careful control so that it adopts a certain identity and performs a specific function. However, if the cell’s DNA is damaged, these internal instructions may get jumbled. A cell that was once a skin cell doing its job to produce pigment may loose this control and instead start dividing and dividing and dividing, forming a tumor. These cells may no longer have the identity of skin cells, and they can invade other tissues of the body in a process called metastasis. This loss of cell control and cell identity is the cellular basis of cancer.

Given the potentially serious outcomes of DNA damage, molecular biologists are extremely interested in understanding it and have been studying it for decades. Luckily cells have a lot of systems in place to detect damaged DNA and repair it. Stay tuned for my next post to hear more about that!