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Replication of DNA

Replication of DNA takes place in the cell nucleus and occurs in the first stage of cell division (interphase).

 At first, the two strands of the parent DNA molecule separate by breaking the hydrogen bonds between the complementary bases. As a result the strands unwind. The place where the two strands separate is called the replication fork.

 Then, according the base-pairing rules, each nucleotide in the two strands attaches a specific, complementary nucleotide that has been produced earlier by the cell and was floating within the cell. That means A attaches to T and G attaches to C. Therefore each strand of the parent DNA molecule acts as a template for the formation of the new complementary strand and directs the synthesis of the new strand.

 After that, the nucleotides between the old strand and the new strand are joined by hydrogen bonds and this forms the "ladder steps" of the new DNA molecule.

 At the same time as the complementary nucleotides are fitted in the right places, the DNA polymerase, an enzyme, join them together by bonding the phosphate group and the sugar molecule of the two adjacent nucleotides. This forms the "handrail" of the DNA molecule.

 This process, DNA replication, continues until all the nucleotides on the templates have joined with the appropriate free nucleotides and two identical molecules of DNA are formed.


  Replication of DNA  
  Created by Ourselves  



This replication of DNA is also known as semiconservative DNA replication as the two old strands are conserved and each serves as a template for the new strand to form. Each of the two new daughter DNA molecules consists of a strand of the parent molecule and a newly synthesized strand.

In human, DNA replication can occur at a rate of 50 nucleotides per second. Do you think it is fast or slow?

DNA replication seems so simple, doesn't it? But actually, it is a very complicated process. What I have just told you is a simplified version, as I want you to first have some ideas about DNA replication. I don't want to scare you away in the beginning of the article. Now here comes the complex version. I am sure you can manage and you have the curiosity and the wisdom to know and understand. Let's go!

There are some rules for DNA polymerase to add nucleotides. Do you still remember a deoxyribonucleotide contains deoxyribose, which is a five-sugar molecule?

"Each nucleotide contains three parts which are deoxyribose, a phosphate group and a nitrogenous base." - from the article "Structure of DNA"

"Deoxyribose is a five-carbon sugar molecule. The five carbon atoms are designated 1', 2', 3', 4' and 5'." - from the article "Structure of DNA"

The truth is that the enzyme DNA polymerase can only add new nucleotide to the 3'-OH group of an already paired nucleotide. Because of this, two restrictions are created. Firstly, A chain of nucleotides can only be extended in one way, the 5'-->3' direction. Secondly, DNA polymerases cannot initiate DNA synthesis on a template of single-stranded DNA.

Then it's impossible for DNA replication to occur!

Don't worry! There's a solution. There is another enzyme called RNA polymerase which is able to add ribonucleotides to a template of single-stranded DNA that has not been paired with any nucleotide. I think you can still remember that RNA and DNA have very similar structures. So ribonucleotides are able to pair with deoxyribonucleotides to form a double-stranded DNA-RNA hybrid molecule. The segment of RNA added by primase, a kind of RNA polymerases, to initiate DNA synthesis is called primer. Primer usually contains 10 to 60 nucleotides. Ribonucleotide also has a 3'-OH group, so DNA polymerase can now add deoxyribonucleotides to continue creating a double-stranded DNA molecule.

Is that all? No, we now still have to face another problem. In the article "Structure of DNA", I have explained that DNA strands are antiparallel. So only one strand has its 3'-OH group facing the replication fork. That's why only one of the two strands can be synthesized continuously. As the replication fork proceeds, DNA polymerase can still add new nucleotides continuously along this strand. The new DNA strand that is synthesized continuously is referred as the leading strand.

How about the other strand? The 3'-OH groups of the newly added nucleotides are facing away from the replication fork, so DNA synthesis has to proceed in the opposite direction to the movement of the replication fork. As the replication fork moves ahead, more nucleotides of this strand are exposed but this section cannot be used as a template as the previous primer has a 5'-phosphate group facing the replication fork. This problem can be solved until a new primer is added. Therefore, this strand has to be synthesized in fragments and discontinuously. The fragments of DNA are called Okazaki fragments. Hence, this strand is called the lagging strand.

Since one DNA strand is synthesized continuously and the other is synthesized discontinuously, thus the replication of DNA can also be called as semidiscontinuous DNA replication.

Hey! The newly synthesized strands are not pure DNA. It still contained RNA primers.

Oh! Sorry, I have almost forgotten about it. The RNA primers must be removed and replaced by DNA. Another type of DNA polymerase and ligase, also an enzyme, will do this job. But another problem arises again. Can you think of it?

At the end of a linear DNA molecule where there is a primer to initiate DNA replication, when the primer is removed, DNA polymerase cannot fill the gap as there is no 3'-OH group for the DNA polymerase to add nucleotide on. Because of this, the telomere becomes shorter and shorter as DNA replication repeats. This problem is known as the linear DNA replication paradox. When the telomere becomes too short, the DNA molecule will stop to replicate and the cell cannot divide anymore.

But in order to pass on the full version of genetic information to the next generation, there is an enzyme called telomerase in the sex cells to overcome the linear DNA replication paradox. Telomerase extends the end of the original strand so that the part that is lost is actually the extended part of the original DNA, which is useless.

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