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Speed and precision of DNA replication | Biomolecules | MCAT | Khan Academy


3m read
·Nov 11, 2024

In the earlier video on DNA replication, we go into some detail about leading strands and lagging strands and all of the different actors, all of these different enzymatic actors. But I left out what is probably the most mindboggling aspect of all of this, and that's the speed and the precision with which this is actually happening.

As we talked about in that video, it feels pretty complex. You have this topoisomerase that's unwinding things; the helicase is unzipping it. Then you have the polymerase that can only go from the 5' to 3' direction. It needs a little primer to get started, but then it starts adding the nucleotides. On the lagging strand, you have to have the RNA primer, but then it's going in, it's going from once again from 5' to 3'. So you have these Okazaki fragments and all of this craziness that's happening.

Remember, these things don't have brains; these aren't computers. They don't know exactly where to go. It's all because of the chemistry. They're all bumping into each other and reacting in just the right way to make this incredible thing happen.

Now, what I'm about to tell you is really going to boggle your mind because this is happening incredibly fast. DNA polymerase has been clocked, at least in E. coli, at approaching 1,000 base pairs per second. I think the number that I saw was 700-something base pairs per second. So polymerase—let me write this down; this is worth writing down because it's mindboggling. It gives you a sense of just how amazing the machinery in your cells is.

So, it's been as high as... and it can change; it can speed up and slow down, and that's actually been observed. But it rates as fast as 700 plus base pairs per second. If this, on this diagram, man, it's just zipping. It's just zipping along. At least from our perceptual frame of reference, a second seems like a very short amount of time to us, but at a molecular scale, these things are just bouncing around and just getting this stuff done.

Now the second thing that you might be wondering: okay, this is happening fast, but surely that has a lot of errors. Well, the first thing you might say is: well, if I had a lot of errors, that would really not be good for biology because you always have DNA replicating throughout our lives. At some point, you just have so many errors that the cells wouldn't function anymore.

So lucky for us, this is actually a fairly precise process. Even in the first pass of the polymerase, you have one mistake—let me write this down because it's amazing—one mistake for every approximately 10 to the 7th. So this is 10 million nucleotides. And that might seem pretty accurate, but you've got to remember we have billions of nucleotides in our DNA. So this would still introduce a lot of errors.

But then there is proofreading that goes back and makes sure that those errors don't stick around. Once all the proofreading takes place, it actually becomes one mistake—one mistake for every approximately 10 to the 9th nucleotides.

So, approximately, you can do this at an incredibly fast pace, as fast as 700 plus, approaching 1,000 base pairs per second. And you have one error for every billion nucleotides, especially after you go through these proofreading steps.

It's incredibly fast; it's incredibly precise. So hopefully, that gives you a better appreciation for just the magic that's literally happening. Look at your hand, or just think about this: it's happening in all of the cells, or most of the cells, of your body as we speak.

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