16 June 2021

Overthrowing the basics

A new discovery has refuted the foundations of modern cell biology

Georgy Golovanov, Hi-tech+

For cell reproduction, the mechanism of synthesis of nucleic acid polymers is used. It is believed that DNA polymerase and RNA polymerase enzymes act only in one direction: they copy DNA into DNA or RNA. This prevents unnecessary corrections to the genome cookbook. However, researchers from the USA have found the first evidence that RNA segments can be written back into DNA. This discovery can affect many areas of biology. In particular, this may mean that RNA can be used as a template for repairing or rewriting the genome.

The team of Professor Richard Pomerantz from Thomas Jefferson University investigated an unusual theta polymerase. Of the 14 DNA polymerases in mammalian cells, only three do most of the work of copying the entire genome in preparation for cell division. The remaining 11 are mainly engaged in the search and troubleshooting of DNA chains. Theta polymerase repairs DNA, but makes a lot of mistakes, according to a press release from Thomas Jefferson University Discovery Shows Human Cells can Write RNA sequences into DNA.

Article by Chandramouly et al. poly reverse transcribes RNA and promotes RNA-templated DNA repair published in the journal Science Advances – VM.

Scientists have noticed that some of these errors manifest themselves in another cellular mechanism, more common in viruses – reverse transcriptase. After conducting a series of elegant experiments, they tested theta polymerase on reverse transcriptase in HIV. And they proved that theta polymerase is able to convert RNA messages into DNA, and does it better than when it copies DNA into DNA.

She was more efficient and made fewer mistakes when she used an RNA template to record new DNA messages than when she feasted DNA into DNA. It can be assumed that this is its main function in the cell.

Using X-ray crystallography, scientists determined its structure and found that this molecule can change shape, adapting to larger RNA molecules. This is a unique property for polymerases.

"Our study indicates that the main function of theta polymerase is reverse transcriptase," Pomerantz said. In healthy cells, the purpose of this molecule is to repair DNA with RNA. In patients, for example, in cancer, theta polymerase ensures the growth of tumor cells and resistance to drugs.

Scientists from the USA have figured out the work of the cellular process, which until today remained a mystery to scientists, although it was described in biology textbooks – how exactly the copying of genetic material that has begun is turned off. This discovery directly concerns the most important process – the transcriptional phase of gene expression.

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