Write RNA back to DNA to see how the polymerase retrogrades

It is known that cells can copy DNA into a new set of DNA, and then enter a newly formed cell. Among them, a type of cellular "machines" called polymerases are involved. They can also construct RNA information, and the information copied from the central library of DNA can be "interpreted" as proteins more effectively. But the polymerase is believed to act only in the direction of DNA to DNA or DNA to RNA, thereby preventing RNA information from being rewritten back into the DNA central bank. Now, researchers have demonstrated for the first time that RNA can also be written back to DNA, which challenges the core laws of biology. Related papers were recently published in "Science Progress".

  "This work has opened the door to many studies and helped people understand that there is a mechanism in their cells that converts RNA information into DNA. Human polymerase can efficiently accomplish this task, but it also creates many problems." Richard Pomerantz, associate professor of biochemistry and molecular biology at Thomas Jefferson University, said this discovery shows that RNA information can be used as a template to repair or rewrite DNA.



  The Pomerantz team first studied an unusual polymerase, polymerase theta. Of the 14 DNA polymerases in mammalian cells, only 3 are responsible for most of the work of replicating the entire genome in preparation for cell division. The remaining 11 are mainly involved in detecting and repairing DNA strand breaks or errors.

  Generally, polymerase can repair DNA, but it will produce many errors or mutations. The researchers noticed that some of the "bad" properties of polymerase theta are shared with another type of enzyme, although the latter is more common in viruses-reverse transcriptase. For example, HIV reverse transcriptase is similar to DNA polymerase, but can bind RNA and read RNA back into the DNA strand.

  Therefore, the researchers tested the relationship between polymerase θ and HIV reverse transcriptase and proved that polymerase θ can convert RNA information into DNA, and the effect is comparable to HIV reverse transcriptase. They said that polymerase θ is more efficient when using RNA templates to write new DNA information than when copying DNA in DNA, and it introduces fewer errors, indicating that this may be its main function in cells.

  After that, the team worked with researchers from the University of Southern California to use X-ray crystallography to define the structure of polymerase θ and found that this molecule can change its shape to fit larger RNA molecules. This feature is found in polymerases. Unique.

  "Our research shows that the main function of polymerase θ is to act as a reverse transcriptase." Pomerantz said, "In healthy cells, it may be used for RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, Polymerase θ is highly expressed, which promotes the growth and drug resistance of cancer cells. It is exciting to understand how the activity of polymerase θ on RNA promotes DNA repair and cancer cell proliferation.” (Tang Yichen)


Author ;Zhao Yuhao

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