MadSci Network: Biochemistry

Re: Why doesn't adenine bond with cytosine in DNA replication?

Date: Fri Nov 2 18:17:21 2001
Posted By: Michael Onken, MadSci Admin
Area of science: Biochemistry
ID: 1004496404.Bc

I need to answer my 6th graders' question why A and T and C and G only bond to each other in DNA replication. I am a non-science major teaching middle school science. Help!

The short answer is, "they don't." A longer answer would be that while these are the preferred, and thus most common, pairings, others do exist. So, in a way, there are two questions: why are A:T and G:C the preferred pairings; and what roles do the other pairings play in the cell? Before answering these questions, here are two excellent tutorials on alternative basepairings:

If you go to the above sites, you will see that there are several other alternatives to the traditional Watson-Crick (WC) basepairs, including Hoogsteen, Wobble, homopurine, homopyrimidine, and even some base-triplets! In each case, the major considerations for any basepair are how many hydrogen bonds are created, and how well does the basepair fit into the rest of the DNA helix. Without getting too technical, there are various thermodynamic and steric considerations that drive the formation of basepairs, such that the most stable pairing will have the most hydrogen bonds with the best fit. In the context of the DNA double helix, A fits better with T than any other base, and G fits better with C than any other base - that is to say, that the A:T and G:C basepairs each have more hydrogen bonds and better fit in the helix than any other combinations. The result of this thermodynamic favorability appears during DNA replication. As the free deoxynucleotides are lining up along the single-stranded DNA template they don't simply sit down, but are constantly binding to and separating from the template. This continual on/off activity is referred to as a chemical equilibrium, and the proportion of [on]/[off] is defined by an equilibrium constant, which is determined by its thermodynamic properties. In short, this means that the more favorable a pairing is, the more time that deoxynucleotide will spend bound to the DNA; so that, by the time the DNA polymerase complex gets to that part of the sequence, this most favorable pairing has the greatest chance of being included in the new strand.

As you've probably guessed from the above, relying on chemical competition to determine basepairing means that there is a pretty good chance that a replicating DNA strand will have several base mismatches where one of these alternative basepairings was occuring when the polymerase came through. The result of these alternative basepairs is a bulge or pucker in the double helix. In almost all organisms, there are special DNA-repair enzymes that follow the polymerase looking for bulges and puckers, which these enzymes remove and replace with, hopefully, the correct deoxynucleotide. So, one of the ways that alternative basepairings are important is that they are the source of most of the mutations that occur in the cell - the mutation rate of an organism being directly related to the efficiency of the DNA-repair machinery that removes these mismatches. In fact, many viruses and bacteria do not have these DNA-repair enzymes specifically as a way of vastly increasing their mutation rates.

The other way that different basepairings are important to the cell requires leaving the DNA behind and looking at the other, more prevalent nucleic acid, RNA. RNA comes in many sizes and shapes and serves many functions, and RNA is considered to be single-stranded because each strand exists in the absence of a complete complementary strand (like DNA). However, RNA is rarely seen as a linear strand: like tRNA (pictured here), most RNA's have extensive basepairing between parts of the same strand, producing helical stems-and- loops, knots, and other, more complex structures. Moreover, helical RNA strands form an A-helix, which differs in size and shape from the familiar B-helix of double-stranded DNA. The A-helix has different spatial characteristics than the B-helix, making some of the alternative basepairings more favorable than in DNA; furthermore, the existence of uracil, instead of thymine, in RNA changes the hydrogen bonding characters of many of the non-WC pairings. In fact, much of the functionality of tRNA, rRNA, and the snRNA's comes from using Hoogsteen basepairing, Wobble basepairing, and base-triplets to form their elaborate structures.

To sum up: in DNA, non-WC basepairing occurs and can be a source of mutations if it is not corrected by the cell's DNA-repair machinery; in RNA, non-WC basepairing occurs relatively frequently and actually plays an important role in several RNA's functions. I hope I didn't get too deep into the technical jargon - there is always a trade-off between lucidity and brevity in science, and I'm the first to admit some of my posts have neither.


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