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Human cells: RNA to DNA is possible

The polymerase enzyme helps our cells repair DNA damage. Contrary to popular belief, it can also convert RNA into DNA.

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Kamal S. has been Journalist and Writer for Business, Hardware and Gadgets at Revyuh.com since 2018. He deals with B2b, Funding, Blockchain, Law, IT security, privacy, surveillance, digital self-defense and network policy. As part of his studies of political science, sociology and law, he researched the impact of technology on human coexistence. Email: kamal (at) revyuh (dot) com

The surprising ability of a human enzyme calls into question dogma

According to popular belief, the polymerase enzymes in our cells can only translate DNA into RNA, not the other way around. But this is obviously a mistake, as experiments now show. 

The human enzyme polymerase theta can also copy RNA into DNA and thus works in a similar way to the enzymes of some viruses. This previously unrecognized ability of the polymerase could explain how genetic fragments of the coronavirus get into our DNA in the event of an infection.

Different types of polymerases are responsible in cells for replicating DNA for cell division, repairing damage in it, and translating DNA into RNA, which then serves as a blueprint for proteins. 

Until now, it was assumed that the polymerases always needed DNA as a template, which they then rewrite to DNA or RNA. The reverse direction – RNA to DNA – is known from some viruses that use an enzyme called reverse transcriptase for this. The HIV virus, for example, converts its own RNA into DNA in order to smuggle it into the human genome.

Undetected side effect of polymerase

A team led by Gurushankar Chandramouly from Thomas Jefferson University in Philadelphia has now demonstrated for the first time that a human polymerase can also translate RNA segments back into DNA. The so-called polymerase theta is actually responsible for repairing DNA damage, but it makes an unusually large number of mistakes. In contrast to other polymerases, it lacks a proofreading function – a property that it shares with reverse transcriptases.

“That is why we hypothesized that polymerase theta is capable of RNA-dependent DNA synthesis,” the researchers write. They tested this hypothesis in a series of experiments. To do this, they compared the functionality of the polymerase theta with the reverse transcriptase of HIV. And indeed: polymerase theta was able to translate RNA into DNA just as well as the HIV enzyme.

RNA master copy against DNA damage

“The fact that a human polymerase can do this with great efficiency raises many questions,” says Chandramouly’s colleague Richard Pomerantz. 

This work opens the door to many other studies that will help us understand the importance of a mechanism for converting RNA messages into DNA in our own cells.

A possible function could be that RNA fragments help to reconstruct missing pieces in damaged DNA. In the tests, Polymerase theta worked more efficiently and caused fewer errors when using an RNA template to write new DNA messages than when copying DNA into DNA. 

This suggests that the main function of the polymerase theta is to act as a reverse transcriptase

says Pomerantz.

With the help of X-ray crystallography, the researchers examined the structure of the polymerase theta. 

The result: Depending on whether it uses RNA or DNA as a template, polymerase theta fundamentally changes its structure. According to the researchers, this ability is unique among polymerases and apparently enables polymerase theta to perform a hybrid function in which it combines the properties of polymerase and reverse transcriptase.

Is this how does coronavirus genetic material get into our DNA?

The discovery of this new ability of the polymerase could possibly explain an observation made during the corona pandemic: A study recently showed that fragments of the coronavirus genome are also found in our DNA – even though Sars-CoV-2 differs from, For example, HIV does not have its own reverse transcriptase. In view of the new results, it now seems possible that the polymerase present in our own cells copied the viral RNA into DNA and thus enabled the integration of these viral genetic material fragments into our DNA.

However, researchers consider it unlikely that the information from mRNA vaccines could also find its way into the human genome. This is because a so-called primer is always required to start reverse transcription, to which the enzyme can attach. 

Chandramouly and colleagues also added appropriate primers for all experiments so that polymerase theta translated the desired sequences. The vaccines do not provide such a start sequence and therefore, according to the current state of knowledge, do not offer any starting point for polymerase theta or reverse transcriptase.

Approach to cancer therapies

However, the results could be of greater importance for cancer research, among other things. While polymerase theta is rarely found in healthy cells, it is strongly expressed in cancer sites. It has previously been associated with cancer cell growth and resistance to chemotherapy drugs. It is therefore a possible target for future cancer therapies.

It will be exciting to further understand how the activity of the polymerase theta on RNA contributes to DNA repair and the proliferation of cancer cells

says Pomerantz.

Source: Thomas Jefferson University

Image Credit: Getty

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