Demystifying Rule-Defying DNA Polymerases

A team of scientists in Taiwan has uncovered how a viral DNA polymerase breaks the golden Watson-Crick rule.

AsianScientist (Apr. 8, 2014) – A team of researchers led by Professor Tsai Ming-Daw of Academia Sinica has demonstrated the mechanism by which a certain DNA polymerase flouts the Watson-Crick base-pairing rule.

Replication of DNA occurs in all living organisms and forms the basis of biological inheritance. DNA is formed and replicated through the pairing of the four nucleotides, adenine (A), thymine (T), cytosine (C) and guanine (G) in a specific pattern: A pairs with T and C pairs with G. This is known as the Watson-Crick base-pairing rule. The synthesis of new strands of DNA is facilitated by enzymes called DNA polymerases.

Scientists have long been fascinated by the fidelity of the DNA polymerase reaction — the way in which the pairing rule is invariably followed. However, in recent years scientists have discovered polymerases that do not follow the Watson-Crick rule, and have sought explanations for how these enzymes function.

Recently published in the chemistry periodical Journal of the American Chemical Society, Tsai’s research investigated a DNA polymerase from the African swine fever virus named Pol X. Pol X is unusual because it can get G to pair with itself, on top of following the Watson-Crick rule.

In conventional DNA polymerization, the enzyme firsts binds to the DNA, and only subsequently the free nucleotides. This allows the DNA sequence to determine which nucleotide binds, restricting the binding to nucleotides complementary to the DNA template. The team found, however, that Pol X is able to bind nucleotides in the absence of DNA.

“Kinetic studies suggested that Pol X does not follow the established mechanistic paradigm that DNA polymerases bind DNA before binding to a nucleotide,” Tsai explained.

The results demonstrate the first solution structural view of DNA polymerase catalysis and a novel mechanism for non-Watson-Crick incorporation by a low-fidelity DNA polymerase.

The article can be found at: Wu et al. (2014) How a Low-Fidelity DNA Polymerase Chooses Non-Watson-Crick from Watson-Crick Incorporation.


Source: Academia Sinica; Photo: kyz/Flickr/CC
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