DNA Replication

DNA Replication


Let me lay out the basics:
Since DNA is two complimentary strands, each strand contains the information to specify the other. Thus, it seemed logical from the first time the structure was determined that the two strands would separate and new subunits (deoxyribonucleotides) would be added to make each new strand, using the other old strand as a template. Each new double helix would therefore really be one old strand and one new one.
Here is the basic idea in video. Like most of the videos I will link, these come from the Howard Hughes Medical Institutes (HHMI). Note that this video shows the new strands being made the same for both templates. As we know (and the video alludes), this cannot happen.

The first problem:


So, one strand is the template for the other. New bases are added one at a time via a simple chemical reaction we have talked about, mediated by a complicated enzyme machine (comprising many different proteins).
The problem is that the chemistry requires that a new subunit can only be added to the 3’ end. So, if you are moving along a replication fork, one strand cannot be replicated easily…the fork is moving the wrong way and it has to be replicated “backward.”
Here’s a more basic video that shows you how an Origin of replication might work and some detail, but in a much simpler form.
Here are two other videos
here and here that have merit, though all of them, including the cool one below, have errors in them.

Notice that there is a second problem.
As the video says, you need a short RNA primer to begin each section when synthesizing the lagging strand. This is put down by an enzyme called “primase.” The leading strand needed an RNA primer to get started too. But, since it is replicated continuously, it only needs one primer, way back at the start of replication.
Here is a link to the really cool video. I think you should look at it again, now that you have seen the simple one. We have to name all the enzymes and talk more about details tomorrow.

Here are the details of the problem


The unit of DNA polymerization (Synthesis) is a deoxyribonucleoside triphosphate. In the image, the “Base” would be either A, T, C or G, depending on what was on the template strand. Just like ATP, these molecules have high-energy (unstable, that is) bonds joining the phosphates. This can therefore be used in transfer reactions, just like enzymes transfer phosphates from ATP in reactions we have studied. There is a seemingly subtle change: instead of the third (
𝛄 or “gamma”) phosphate on the end being attacked by the OH on the 3' carbon, the first one is (called “α”). This change has a big impact, though. It links the 3' carbon of the existing DNA to the 5' carbon of the incoming base via a phosphate.
This is called a “phosphodiester.”

dNTP
Here is a specific example, deoxyATP
dATP
The next base that comes in will use the high-energy triphosphate it carries to attack the 3' OH.
TransferReaction
And forms this:
Dinucleotide

Thus, as we said, we must add DNA to the growing 3' end. From a chemical standpoint, there isn’t any reason why you cannot add an incoming base to the 5' end, provided that end has a 5' triphosphate. That triphosphate would be unstable, however. Should it hydrolyze, the new DNA wouldn’t be made until another enzyme came in and “recharged it” with new phosphates.