Cells contain machines that duplicate DNA in a new set that goes into a newly formed cell. This same class of machines, called polymerases, also build RNA messages that are like notes copied from the central DNA repository of prescriptions so that they can be read more efficiently into proteins. But polymerases were thought to act in only one direction, DNA in DNA or RNA. This prevents the RNA messages from being re-recorded in the genomic DNA recipe book. Researchers at Thomas Jefferson University are now providing the first evidence that RNA segments can be written back into DNA, potentially challenging the central dogma of biology and can have far-reaching implications affecting many areas of biology.
“This work opens the door to many other studies that will help us understand the importance of having a mechanism for converting RNA messages into DNA in our own cells,”
The work was published on June 11 in the journal Scientific progress.
Together with the first author, Gurushankar Chandramuli, and other collaborators, Dr. Pomerantz’s team began researching a very unusual polymerase called polymerase theta. Of the 14 DNA polymerases in mammalian cells, only three do most of the work of duplicating the entire genome to prepare for cell division. The other 11 are mostly involved in detecting and repairing when there is a break or error in the DNA strands. Theta polymerase repairs DNA, but is very susceptible to errors and makes many errors or mutations. Therefore, the researchers note that some of the “bad” properties of theta polymerase are those that it shares with another cellular machine, although more common in viruses – reverse transcriptase. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase, but can also bind RNA and read RNA back into the DNA strand.
In a series of elegant experiments, the researchers tested polymerase theta against HIV reverse transcriptase, which is one of the best studied of its kind. They showed that theta polymerase is able to convert RNA messages into DNA, which it does, as is HIV reverse transcriptase, and that it actually does a better job than duplicating DNA in DNA. Polymerase theta is more efficient and introduces fewer errors when using an RNA template to write new DNA messages than when duplicating DNA in DNA, suggesting that this function may be its primary purpose in the cell.
The team collaborated with the laboratory of Dr. Xiaojiang S. Chen at the USC and used X-ray crystallography to determine the structure and found that this molecule was able to change shape to accommodate the larger RNA molecule – a unique feat among polymerases.
“Our research shows that the main function of theta polymerase is to act as a reverse transcriptase,” says Dr. Pomerantz. “In healthy cells, the target of this molecule may be RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, theta polymerase is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to find out more. further, the activity of theta polymerase on RNA contributes to DNA repair and cancer cell proliferation. ”
The study identifies an unprecedented dual function in the enzyme critical for cancer growth
Polθ reverse transcribes RNA and promotes DNA repair with a template Scientific progress (2021). DOI: 10.1126 / sciadv.abf1771
Provided by Thomas Jefferson University
Quote: A new discovery shows that human cells can write RNA sequences into DNA (2021, June 11), retrieved on June 11, 2021 from https://phys.org/news/2021-06-discovery-human- cells-rna-sequences.html
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