What are you going to learn?

  • What is DNA replication?
  • How does DNA replicate?
  • What does it mean that DNA replication is semi-discontinuous and semi-conservative?
  • What enzymes are involved in DNA replication?
  • terms: replicon, replication origin, replication fork, template strand, leading strand, laggging strand, Okazaki fragments, proofreading, helicase, single-stranded binding proteins, DNA polymerase, RNA primer, primase, DNA ligase

DNA replication is a process in which the DNA molecule duplicates producing two molecules of DNA from the original one DNA molecule. This process is needed when cells duplicate, for example, as each needs its own copy of DNA.

blue - original DNA, red - newly synthesized DNA

In eukaryotic cells, DNA replication does not happen at only spot of the DNA, but at several at once. The small parts are called replicons and their beginning, at which the replication starts, a replication origin. In prokaryotes, the situation is completely different.

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DNA replication happens at several spots at once. These spots are called replicons and they each have their replication origin.

Replication starts by the two DNA strands unwinding and separating. This is possible because of a special enzyme called helicase which breaks the hydrogen bonds between the two strands. Once the two DNA strands are separated, single-stranded binding proteins (SSBs) bind to the two strands to prevent them from joining back together. The structure that forms when the two DNA strands separate is called a replication fork.

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Helicase breaks the hydrogen bonds between the DNA strands and separates them.
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SSBs bind to DNA strands to prevent them from joining back together.

After the separation, the two strands are now ready to be duplicated. They are each going to work as a template by which the complementary strand is going to be synthesized. For that reason, we call them template strands.

The special enzyme that synthesizes the new strands by adding new nucleotides to it is called DNA polymerase. DNA polymerase follows the basic base-pairing rules (A-T, C-G) to ensure that the two strands are complementary. The problem is, however, that DNA polymerase cannot synthesize the new strand out of nowhere. It needs a short RNA sequence called RNA primer to know where to start. This short sequence is synthesized by an enzyme called primase.

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Primase synthesizes a short RNA sequence called primer, which allows DNA polymerase to work properly.

Another problem is that DNA polymerase can synthesize the new DNA strand in the 5'-to-3' direction only. Because the two DNA strands are antiparallel, each strand is going to be synthesized in a different manner. One is going to be synthesized continuously, as the DNA polymerase will simply move in the 5'-to-3' direction, and we refer to this strand as the leading strand. The other is going to be synthesized discontinuously, in small pieces, because the DNA polymerase has to shift every time that helicase separates another part of DNA to work in the 5'-to-3' direction as can be seen in the picture below. This DNA strand is referred to as the lagging strand and the small DNA pieces are called Okazaki fragments. These Okazaki fragments are later connected by another enzyme called DNA ligase. We say that DNA replication is semi-discontinuous as one DNA strand is synthesized continuously and the other discontinuously.

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DNA polymerase adds new nucleotides in the 5'-to-3' direction only. For that reason, one strand (leading strand) is synthesized continuously, and the other (lagging strand) discontinuously. This is why DNA replication is said to be semi-discontinuous.
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DNA ligase connects Okazaki fragments on the lagging strand.

What is also fascinating is that DNA polymerase is capable of proofreading. This means that the enzyme checks that a correct nucleotide with the correct base has been added. This eliminates the possibility of making a mistake, which, considering how long the DNA is, is amazing.

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DNA polymerase is capable of proofreading. This ensures that DNA polymerase makes as few mistakes as possible.

Because the newly synthesized DNA is going to contain one original DNA strand (the template) and one new strand, we say that DNA replication is semi-conservative (half of the molecule is "old" and half "new).

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DNA replication is semi-conservative as the new DNA molecules contain one "old" and one "new" strand.

References:
Alberts, B. (2014). Essential Cell Biology. Garland Science.
Cooper, G. M., & Hausman, R. E. (2007). The cell: A molecular approach. ASM.
Pollard, T. D., Earnshaw, W. C., Lippincott-Schwartz, J., & Johnson, G. T. (2017). Cell biology. Elsevier.
Snustad, D. P., & Simmons, M. J. (2012). Principles of Genetics. Wiley.