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Human cells can write RNA sequences into DNA

Polymerases enzyme in cells duplicate DNA into a new set that goes into a newly formed cell. The same enzyme also builds RNA messages to be read by proteins.

It has been thought that polymerases work in a unidirectional manner: DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA.

A new study contradicts this belief and suggests that RNA segments can be written back into DNA. Undoubtedly, the study is quite shocking, which potentially challenges the central dogma in biology and could have wide implications affecting many fields of biology.

Scientists from the Thomas Jefferson University started this study by focusing on very unusual polymerase, called polymerase theta. Polymerase theta repairs DNA but is very error-prone and makes many errors or mutations.

Scientists observed that some of polymerase theta’s “bad” qualities were ones it shared with another cellular machine, albeit one more common in viruses — the reverse transcriptase. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase but can also bind RNA and read RNA back into a DNA strand.

Through experiments, scientists tested polymerase theta against the reverse transcriptase from HIV, one of the best-studied of its kind. They showed that polymerase theta was capable of converting RNA messages into DNA, which it did, and HIV reverse transcriptase, and that it did a better job than when duplicating DNA to DNA.

Polymerase theta was more proficient and presented fewer errors when using a RNA template to compose new DNA messages than copying DNA into DNA, recommending that this function could play its essential role in the cell.

Then by using x-ray crystallography, scientists were able to define the structure and found that this molecule could change shape to accommodate the more bulky RNA molecule — a feat unique among polymerases.

Richard Pomerantz, Ph.D., associate professor of biochemistry and molecular biology at Thomas Jefferson University, said, “Our research suggests that polymerase theta’s main function is to act as reverse transcriptase. In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to understand further how polymerase theta’s activity on RNA contributes to DNA repair and cancer cell proliferation.”

Journal Reference:
  1. Gourishankar Chandramouly et al. Polθ reverse transcribes RNA and promotes RNA-templated DNA repair. Science Advances, 2021; 7 (24): eabf1771 DOI: 10.1126/sciadv.abf1771

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