![]() ![]() It will be exciting to further understand how polymerase theta’s activity on RNA contributes to DNA repair and cancer-cell proliferation.” In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. “In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. “Our research suggests that polymerase theta’s main function is to act as a reverse transcriptase,” says Dr. Chen’s lab at USC and used x-ray crystallography to define the structure and found that this molecule was able to change shape in order to accommodate the more bulky RNA molecule - a feat unique among polymerases. Polymerase theta was more efficient and introduced fewer errors when using an RNA template to write new DNA messages, than when duplicating DNA into DNA, suggesting that this function could be its primary purpose in the cell. They showed that polymerase theta was capable of converting RNA messages into DNA, which it did as well as HIV reverse transcriptase, and that it actually did a better job than when duplicating DNA to DNA. In a series of elegant experiments, the researchers tested polymerase theta against the reverse transcriptase from HIV, which is one of the best studied of its kind. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase, but can also bind RNA and read RNA back into a DNA strand. The researchers therefore noticed 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. Polymerase theta repairs DNA, but is very error-prone and makes many errors or mutations. The remaining 11 are mostly involved in detecting and making repairs when there’s a break or error in the DNA strands. Of the 14 DNA polymerases in mammalian cells, only three do the bulk of the work of duplicating the entire genome to prepare for cell division. Pomerantz’s team started by investigating one very unusual polymerase, called polymerase theta. Together with first author Gurushankar Chandramouly and other collaborators, Dr. The work was published June 11th, 2021, in the journal Science Advances. “The reality that a human polymerase can do this with high efficiency, raises many questions.” For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA. “This work opens the door to many other studies that will help us understand the significance of having a mechanism for converting RNA messages into DNA in our own cells,” says Richard Pomerantz, PhD, associate professor of biochemistry and molecular biology at Thomas Jefferson University. ![]()
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