Nucleic Acid Structures

I was anticipating a brief expedition to the fridge, but instead, Sapphire and I got wrapped up in our respective complaints about the unendearing quirkiness of cellular processes. Now I have returned, stolen apple juice in hand, to give you details you didn’t need to know about DNA.

Let’s do this thing!

DNA is a double helix. This is something that virtually everyone knows from an early age. If you’ve had high school biology, you also know that it has complementary strands, and those strands are antiparallel (running in opposite directions).

However, DNA is by no means a static molecule. In addition to being flexible by nature (I mean, it’s like, a molecular thread. We literally wind it around spools to store it), its constituent parts can move quite easily. Deoxyribose sugars can pucker at either the third (3′) or second (2′) carbon, and either toward the phosphate-base plane (endo) or away (exo). Bases can rotate about their bonds (syn or anti). So can phosphates and oxygens.

In fact, the structural integrity of DNA as a helix is due entirely to a molecular game of “I’m not touching you!” Hydrogen bonds loosely tether bases on opposite strands together, forming the familiar rungs of the DNA ladder. Negative phosphates maximize their personal space using the structure of the helix. Base pairs stack together to avoid the disgusting water surrounding the molecule.

Now, it’s worth noting that, when two bases form a base pair in a double helix, the bonds holding them to their sugars aren’t directly across from each other. This ultimately means that the helix twists up into a shape where parts of the backbone are closer to each other than others, making a major groove and a minor groove.

Our typical vision of DNA is probably of DNA in its most common conformation, B-DNA. B-DNA is a modest-looking form of DNA, with distinct major and minor grooves and a nice, smooth backbone. One helical turn (the helix’s “pitch”) is about 3.4 nm, and consists of about 10-10.6 bp. Its sugars are puckered up in a 2′-endo conformation.

However, there are other forms of DNA. A-DNA, a short, squat form of DNA (also seen in double-helical RNA due to steric hindrance from the 2′-OH) has wider turns that are closer together. Its pitch is about 2.5 nm, with each turn consisting of 11 bp. Bases are tilted at a 19º angle from the perpendicular of the helical axis. Its sugars pucker in a 3′-endo conformation. This forms under dehydrating circumstances.

Z-DNA is freaky weird, which is probably why it’s common SciFi fodder. In Z-DNA, repeating alternations of Cs and Gs cause the guanine nucleotides to do something kind of stupid: they flip 180º on their bond axis. Because they do this, their alternate Cs have to do it, too, but because Cs can’t quite accomplish this properly, they end up turning entirely upside-down (sugar and all). This means that the backbone gets “rolled under,” and it looks zigzagged (thus the “Z”). Z-DNA is left-handed (opposite normal DNA) and thin, and it can occur in stretches of otherwise normal B-DNA.

Outside of these structures, DNA can pull other conformational shenanigans, as well. For example, when inverted repeats occur in the sequence, individual strands of DNA can fold in on themselves, base-pairing with themselves and creating hairpins. When the two strands come together again, they form cruciform structures.

Another really strange trick of DNA shapes comes in when you consider Hoogsteen base pairing, which is essentially base pairing done “backwards.” In other words, the N7 nitrogen of the purine in the base pair participates in hydrogen bonding instead of its “functional group,” leaving its functional side free to bond with another base. This creates base triplets, which give rise to (deep breath) triple-stranded DNA.

But wait! It gets better! In sequences with lots of guanine, the guanines can spiral together using Hoogsteen base pairing to form DNA quadruplexes. These seem horrifying and alien, but really, they’re quite common: in fact, they form in the telomeres of our chromosomes!

Now, with all of these different forms of DNA, you’ve probably guessed that DNA is pretty good at being in a helix. This is quite true! In fact, if you put DNA in a solution that causes its strands to disassociate (“melting”), such as a solution of high temperature or low pH,  and then take the temperature/pH/etc. away again, DNA helices will zip themselves back up without batting an eyelash. This doesn’t have to just happen with DNA from the same source—for example, about 25% of mouse DNA will reanneal with human DNA (meaning that about 25% of our genetic sequences are very similar to those in mice!).

Geez! Who would’ve thought that DNA could adopt so many structures? You’d think it’d get all tangled up, twisting around and bonding with anything that moves. However, we’re just seeing the beginning of DNA’s shenanigans. Just wait until it starts trying to get itself replicated.

Questions? Comments? Feel free to leave them below! I’ll see to them first thing tomorrow freakin’ morning, because I’m going to bed.



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