DNA II – How does DNA replicate itself?

In my previous post DNA I I explained the very basics of DNA. Here I will try to explain one of the most complex processes in life, the replication of DNA. Welcome to the unveiling of one of the greatest mysteries in biology!

DNA has two special properties, it is significantly stable and easy to replicate. As a result, it was chosen by evolution (a topic that will be explained in coming articles) as the biologic information carrier. But first of all, why does DNA have to be replicated?

The cell cycle

Most cells follow a simple cycle, they divide, grow, perform their function (or just live) until they can divide again (Figure 1). Replicating the DNA is the way cells have to give their information to the future generations, to perpetuate their lineage if you will. The relevance of this resides in the concept of evolution which, as I said, will be explained in a future article. Right now, what concerns you is that when cells divide, a process known as mitosis in mammalian cells, and the two resulting cells need to be able to survive. By replicating the DNA, each cell receives a copy of the manual containing all the information required to survive. More or less like a biology survival guide written by Macgyver.

_{Figure 1. The cell cycle. Source: http://schoolbag.info/biology/living/57.html} .

The replication process

The whole replication process is based on the affinity properties of the nitrogenous bases of the DNA. -Wow, science gibberish! If you are lost or you find an unknown technical word along this post, check my previous post, which contains a brief explanation of the concepts mentioned in this post.- Hence, you only need to put an adenine (A) close to a T (thymine) and they will bind together by themselves (magic? No, thermodynamics but we are not going down that rabbit hole…yet).

- Oh that is easy! – Not so fast lad. DNA is very sensitive in a single chain form that is why is always found in a double chain form, because it is a lot more stable (Figure 2). Hence, every single nucleotide is already paired and stable. Even if a matching nucleotide gets close, an already bound couple will not separate and exchange couples. So how did biology solve this problem?

_{Figure 2. DNA in a double helix form. Source: http://www.sciencebuddies.org/blog/2013/04/celebrating-dna-and-the-history-of-the-double-helix.php} .

The replicating machinery

Proteins. The answer is almost always proteins. Remember, proteins are the robots that fulfil DNA orders. Let me introduce you then one of the most, if not the most famous of such robots, the DNA polymerase. This protein acts together with a whole bunch of other proteins to actually open the DNA separating the two chains. Once the chains are open, the DNA polymerase gets in there and starts replicating the DNA. Since now the nucleotides are not couples they are susceptible to be bound to nearby matching nucleotides. Actually, it is more accurate to say that the DNA polymerase smashes them together.

The DNA polymerase not only creates a new chain by adding together one nucleotide after the other one but also checks if it is doing a good job between adding a new nucleotide (Figure 3). A-M-A-Z-I-N-G. It can add close to a thousand nucleotides per second, only making one mistake every 10^(9) nucleotides (1). So almost no mistakes right? WRONG. Question everything!

Take a look at this cool video of how it works!

Errors

You are a replicating mistake, a lucky one. 1 error every 1000000000 nucleotides looks like nothing right?. Let us crunch some numbers:

A human cells contains approximately 1.15·10^(10) nucleotides (1). Hence, every time the DNA of a cell is replicated 11.5 mistakes are made. Now, you began as a single cell, while a human adult body has approximately 3.72 × 10^(13) (2), so something in the order of a thousand billions. * - this numbers are incredibly big, you cannot not picture in your head how a* thousand billions of something looks like. Biology is small but at the same time huge. Amazing -.

If you do the math, you only need around 40 replications to reach that number, but this is not true since there are cells that only divide once, cells that have a lifetime of days… The real number of divisions during a lifetime is close to a quadrillion (1015) according to Wikipedia. Even if the number is not correct, it is a good approximation. Therefore, the total number of replicating mistakes in a lifetime is about 11.5 quadrillions. Good, we should all be dead right? Wrong again.

An error or change in the DNA is known as a mutation. Most of the mutations fall in parts of the DNA that apparently do not encode for anything, thus having no effect. Others will cause changes in proteins that do not affect the function of the protein. From the rest, the majority will kill you, and the ones left will change the color of your eyes, the length of your arms, the shape of your skull, the levels of oxygen that your cells can take in, the facility with which you learn new languages…

Conclusions

The DNA is replicated using proteins that open the double chain helix and create a second copy, hence each of the cells resulting from the division keep a copy. During the replication errors, known as mutations are introduced. This mutations are the basis of EVOLUTION.

Hope you liked the article. Do you have questions? Comment them and see them answered! Just thought about something you would like to know? Ask me. Next article GMOs (lets start a fight!). Follow me to find out more about Biotechnology

Bibliography

1 - Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (1997). Molecular Biology of the Cell (Garland Science, New York, 2002).
2 - Bianconi, E., Piovesan, A., Facchin, F., Beraudi, A., Casadei, R., Frabetti, F. & Perez-Amodio, S. (2013). An estimation of the number of cells in the human body. Annals of human biology, 40(6), 463-471