A short explanation of DNA and its role
Host Amber Smith: Upstate Medical University and Syracuse, New York invites you to be The Informed Patient with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. You may know that DNA holds our genetic information, but there's much more to know and much more to learn about DNA. So I've asked a DNA scientist from Upstate to help us understand the importance of DNA. Dr. Wenyi Feng is an associate professor of biochemistry and molecular biology at Upstate. Her laboratory focuses on the mechanisms of genomic instability induced by DNA replication, and she's more used to teaching medical students, but today she's agreed to answer some basic questions about DNA. Welcome to The Informed Patient, Dr. Feng.
Wenyi Feng, PhD: Thank you for having me.
Host Amber Smith: Do I understand correctly -- each cell in the human body contains 23 pairs of chromosomes, and each chromosome contains many genes, and genes are made up of DNA, is that right?
Wenyi Feng, PhD: I think that's a pretty accurate representation. The only thing I might clarify is that the chromosomes are made of DNA. So not only the gene parts of the chromosome, but the entire chromosome is made of DNA.
Host Amber Smith: I see. Now, how do you describe what DNA is? It's got a long name, I know that.
Wenyi Feng, PhD: Right. So yes, the full name for DNA is deoxyribonucleic acid. That is essentially describing the acid nature of the chemical that makes up the DNA. But in terms of its morphology, if you will, the shape of the DNA, it's really a long polymer. So imagine two strands of your favorite necklace intertwined with each other, right, that can be stretched and also compressed and folded to form 3d shapes. So that's how DNA in our cells, in the most basic form looks like. However, it's not naked. So DNA is actually coded with lots of proteins. That's the chromosomal DNA part of the DNA. The chromosomal DNA describes the composition of DNA together with coding proteins. And so in terms of the final shape in the cells, the DNA is actually compacted. So we want to imagine that the individual polymer, if you stretch it out completely, each cell contains about two meters of this fiber.
Now imagine this fiber has to be compacted so that it can fit into a tiny space of a single cell. That polymer would have to be, first of all, super coiled, which can be likened to extension cord of your computer, when it first comes out of the factory. It's packed in a box. It's neatly coiled, so that it saves space and you can pack it into a tiny box. And so that's the first form of change of the polymers. So it's a super coil, and then those multiple supercoils can be additionally folded to form these loops, which then is interacting with lots of proteins as well. Together they get compacted to become the chromosomal DNA.
Host Amber Smith: So is the double helix -- the twisted strands that we all saw in science class at school -- is that still the best way to think of what DNA looks like?
Wenyi Feng, PhD: Yes. So at the most basic level, that is how the DNA looks like. It is a double helix structure, which is essentially the reason why these polymers can be conducive to super coiling and to have folding to form the compacted molecule. However, I would just emphasize that if you were to just look at the DNA directly under the microscope, you will never see the double helix -- unless you purify the DNA and look it in test tubes. So the duplex DNA is not the directly visible component that one can visualize under the microscope.
Host Amber Smith: Interesting. Is the same DNA in every cell of a person's body?
Wenyi Feng, PhD: In principle, yes. However, let's say the DNA in my liver versus my blood may contain variations, due to the so-called somatic mutation process. That's made up of very different origins in terms of tissue, and they are subject to additional mutations. So while in the germline, meaning while we are still sperms and eggs, our DNA is, there's only that one copy. But once development takes place and we form different organs, DNA in those cells are subject to additional mutations, which will present variations.
Host Amber Smith: Is that because the cells in the blood have different responsibility than the cells and the liver.
Wenyi Feng, PhD: Yes, that's a good way to put it because different tissues and cells in different organs are responsible for very, very different functions in our bodies and are exposed to a different environment and, therefore, have different consequences on their genome changes or maintenance.
Host Amber Smith: How much difference is there from one person's DNA to another person?
Wenyi Feng, PhD: Despite the fact that we're individuals that look very different from each other and behave very different from each other, we are very similar at a genetic level to each other. Over 99% of our DNA are identical between humans, and so it's only that tiny percent of less than 1% the difference that makes us unique.
Host Amber Smith: How different is human DNA from the DNA of other mammals?
Wenyi Feng, PhD: Depending on the species, obviously, I would say overall, there's remarkable similarity between different species of mammals. For instance, we share at least 98% of similar DNA with chimpanzees, right? So that's not much more difference than the individual variation between humans. And, we are also -- I don't have the exact numbers, but I would say -- we're at least 80% similar to cats, and a little less to mice. And then we will be further diverged from other species like reptiles and plants.
Host Amber Smith: Interesting.
This is Upstate's The Informed Patient podcast. I'm your host, Amber Smith talking with Dr. Wenyi Feng. She's an associate professor of biochemistry and molecular biology at Upstate, and she's patiently walking us through an explanation of what DNA is.
So what happens to DNA when cells divide?
Wenyi Feng, PhD: So when cells divide, we need to make a new copy of DNA. That's the foremost requirement for what DNA serves in terms of its purpose. And in addition to that, it also needs to provide a transcript for proteins. So we need to make RNAs in order to make proteins. So DNA is the template for both making additional copy that's completely identical to the original copy. It also serves as a template for making the RNA transcript.
Host Amber Smith: Are there potential mistakes that occur during DNA replication that lead to disease?
Wenyi Feng, PhD: Oh boy. Yes. That is in fact the main interest of my research, which is what happens when DNA replication, this process that's supposed to be very faithful. It makes, for instance -- I'll just give you an idea -- it makes one mistake when copying the DNA code. It makes one mistake in every hundred million nucleotides that are DNA bases that it copies. So it has exceedingly high fidelity, and, I would say, very accurate. But despite that high fidelity, it could still make mistakes. And it's those mistakes that degenerate genomic stability that needs to be taken care of. And we're interested in what happens when those mistakes are not taken care of, what are the consequences to our genome?
Host Amber Smith: I know some of your research focuses on DNA repair. What can you tell us about that? Does the DNA repair itself?
Wenyi Feng, PhD: Yes, the DNA repair itself. So as I was saying, for instance, when the DNA is making a copy of itself and makes one in a hundred million copies ofbases and that is mainly due to the fact that there is a self-correcting machinery, or property of the DNA replication machinery. So as it was copying, it can actually catch the mistakes that it makes and go back and fix it. So, if you were to just look at the most basic accuracy of the machinery, it's not nearly as accurate as one in a hundred million bases. It's far more frequent than that. But it's due to that self-correcting property or function of the machinery, it can boost up its accuracy to that level.
So, even though my lab is not directly studying these repair machinery, we are looking at the relationship between the process of DNA replication and the repair process and how these two complicated pathways interact with each other, interplay with each other.
Host Amber Smith: Now you mentioned RNA. So, can you explain how that's related to DNA?
Wenyi Feng, PhD: Yes. So I sort of alluded to that. RNA is a transcript of DNA. So the best way to describe it is that you've got a recipe book for some product, right? That product bears resemblance to that recipe. So it's not like taking flour to make a cake. The resemblance between the ingredients and the product is much more similar in terms of DNA and RNA. Yet it is a different molecule. It lives in different places. It goes from the nucleus where the DNA lives, and it goes into the cytoplasm to perform additional functions, one of which is that itself serves as a transcript for making proteins. So itself becomes a recipe book. So even though DNA RNA are similar in terms of the fact that they're polymers and they're made up of these nucleotides, even the components have key differences of each other. They're fundamentally different molecules that have very different functions in the cells.
Host Amber Smith: I'd like to understand what remains to be learned from studying DNA. Is there a particular thing or maybe several things that today's DNA researchers are hoping to find or understand?
Wenyi Feng, PhD: That is a great question. So I would say that, despite the fact that we know a whole lot about how DNA replication works and how transcription works, and how they work with each other to maintain the stability of the genome, there are still many fundamental questions that remain unanswered. For instance, one of the key interests in my lab is what happens to DNA when the polymer gets broken? -- which, in fact, is happening more frequently than you might appreciate. The reason why they break is not at least due to the replication process itself. So imagine you're trying to unwind, untangle that ball of polymer that you just compressed into the cells, and you're now trying to detach the proteins that are bound to these DNA, and in order to finally separate the two strands to make room for copying your DNA or transcribing your RNA. That whole process is quite dangerous. If you imagine doing that physically to the ball of polymers. And so it's not surprising that the DNA are prone to breakage. And when it breaks, it's detrimental to the cells if it doesn't get repaired.
So we, for instance, are interested in, first of all, where do these breaks occur in the genome? Because they apparently don't occur at random spots. So they occur at specific locations that all of us have higher propensity to generate breakage. So we're interested in finding where these breaks are occurring and whether they have different tendency to break in blood cells versus liver cells versus kidney cells, and so on and so forth, and ultimately in the central nervous systems, whether these processes differ from each other. And, ultimately by studying where these breaks take place, we hope to understand their impact on genomic rearrangement that ultimately impacts the health of each of those tissues and the overall health of the human being.
Host Amber Smith: As we wrap up, is there one thing you think everyone should know about DNA or some misconception you'd like to clear up?
Wenyi Feng, PhD: I'm not sure if I can think of any misconception at the moment, but, I'd like to go back to the beginning of our discussion where we talked about the difference between human beings that makes us unique. So, despite the fact that it's a small part of our genome, apparently, it's still something, in my mind, very precious to hold on to. It's that unique information that makes us distinct human beings. So I consider that something that we should all respect and treasure. So, I would say when we think of our DNA or the very information that it carries, we need to respect that. We should be aware that it's uniquely our own intrinsic property that we have to be careful who we share that with.
Host Amber Smith: Dr. Feng, this has been very interesting, and I appreciate you making time for this interview.
Wenyi Feng, PhD: Thank you very much. It's been my pleasure.
Host Amber Smith: My guest has been Dr. Wenyi Feng. She's an associate professor of biochemistry and molecular biology at Upstate. The Informed Patient is a podcast covering health, science and medicine brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/Informed. This is your host, Amber Smith, thanking you for listening.