This is the third in a series of explainers on molecular biology topics pertinent to my recently published PhD thesis work. See part 1 about DNA damage and part 2 about damage repair.
As we saw in parts 1 and 2, cells work really hard to protect their DNA. But what is it all for? How is that precious information used to build cells and make entire humans? You may have heard that genes make us who we are. Well, genes are segments of DNA which instruct the assembly of proteins. Proteins are the real workhorses of the cell, they do everything including the cellular processes I talked about in parts 1 and 2. Proteins duplicate the DNA before cell division, they package up the DNA into chromosomes, and repair DNA. Parts of your body outside of the cell like your hair and the surface of your skin are also made of proteins. Proteins are everywhere doing everything!
DNA holds the information to make proteins, but it is too precious to get directly involved in the nitty gritty business of making them. It stays all safe and snug in its own section of the cell called the nucleus, and the genetic information is copied down into a molecule called RNA, which leaves the nucleus and directs the building of proteins. RNA is a molecule very similar to DNA, but it is much more disposable. Once it has done its job to make a protein, it is broken down and its parts are recycled. This process of copying DNA into RNA is called transcription.
Since transcription is so fundamental to and necessary for life, and it seems to be a process put in place to protect DNA, researchers were surprised to find that transcription itself can actually be a source of DNA damage. Over the past decade we have found that RNA can actually invade DNA forming an unstable structure. This RNA-DNA structure can lead to DNA damage, with all the potentially disastrous consequences.
Transcription is constantly happening as cells are always making new RNA and proteins. But this RNA is potentially damaging to the DNA, so what’s a cell to do? Luckily there are back-up systems in place. I studied two proteins called RNase H1 and RNase H2 which can remove the RNA from DNA and resolve the problem. We still aren’t exactly sure how RNA in the DNA causes damage, but cells that lack functional RNase H1 or RNase H2 have a lot of DNA damage, and humans cannot survive without these enzymes. For my work I studied how these two proteins act in similar and different ways to reduce DNA damage. In part 4 of this series I will go into more details about the study.