A new study has revealed that DNA can be assembled in a way we didn't know about before

Scientists have discovered a completely new method of DNA synthesis. Normally, DNA synthesis requires a DNA template that serves as a guide for proteins called DNA polymerases. However, a team from Stanford University has now discovered a new type of polymerase that can function even without a DNA template. In the bacterial defense system, DNA strands (orange and cyan) are synthesized by two enzymes: one (yellow) uses RNA (beige) as a template to guide the assembly of the nucleotide bases that make up DNA. The second and unusual enzyme (light blue) uses its own amino acids as a template. For decades, biology textbooks have stated a simple rule: DNA is created by copying a DNA template. After one enzyme unravels the DNA double helix into two separate strands, another enzyme, called polymerase, creates a complementary sequence for each strand, base by base. Simply put, this creates two copies of the original DNA. This is then translated into RNA, and that into proteins. Scientists refer to this direction of translation as the central dogma.

However, new research into how bacteria defend themselves against viruses now shows that this rule of synthesis is not absolute. In the journal Science, a team from Stanford University in the U.S. describes a bacterial enzyme (DRT) that synthesizes a long repetitive DNA sequence without using nucleic acids from other DNA as a template, instead using its own structure as a guide. “This research is groundbreaking,” says Philip Kranzusch, a biochemist at Harvard Medical School who studies bacterial defense. According to Adi Millman, a biotechnology researcher at MIT, the use of a protein as a template for DNA synthesis is “a significant conceptual shift from the classical central dogma,” in which information flows in one direction from nucleic acids—that is, DNA—to proteins. Although this is not a discovery that will rewrite science textbooks, it certainly adds one—or perhaps even three—interesting new chapters. It has implications for bacterial behavior, biological evolution, and the building blocks of life.

An Unusual Bacterial Defense Mechanism

The main impetus for this study was to investigate defensive reverse transcriptases (DRTs), which bacteria use to fend off viral attacks. Scientists had already observed certain unusual behaviors in these polymerases during DNA synthesis. Specifically, the team cloned the DRT3 system in the bacterium Escherichia coli (E. coli) and examined its behavior both in test tubes and in living cells. In doing so, they uncovered three components of the DNA-synthesis machinery: two enzymes called Drt3a and Drt3b, and a non-coding RNA segment. Drt3b, in particular, proved to be a major surprise, as it was capable of synthesizing new DNA without any template to guide the arrangement of individual nucleotides in the nascent DNA. This is an “all-in-one” mechanism that has never been observed before. “The protein itself serves as a template for the DNA sequence,” explains Stanford biochemist Alex Gao. “That was quite a surprise. It’s a fundamentally new way for life to create DNA.”

What this means for the future

At this point, scientists aren’t entirely sure how bacteria use DRT3 to protect themselves from invading viruses. And while this may seem like a very specific use case, that doesn’t mean we can’t find other ways to apply it. For example, CRISPR also began as a natural defense system in bacteria before scientists adapted it to create a groundbreaking gene-editing technique. In 2020, the Nobel Prize in Chemistry was awarded for the CRISPR method. In the future, there is a possibility that the mechanism used by Drt3b could also be utilized and adapted. While scientists are already working on ways to create synthetic DNA in the lab, the specific Drt3b polymerase that was the subject of this study is engineered as a highly specific form. It will be difficult, though perhaps not impossible, to reprogram it for other purposes. Further studies will be needed to fully understand how DRT3 fends off viral attacks and how bacteria utilize it. These should provide deeper insight into the structure of this type of DNA and its potential applications. The DRT3 system appears to be widespread among bacteria, suggesting that it is not merely a biochemical curiosity. However, how it prevents viruses from attacking bacteria remains a mystery. In a broader context, this discovery underscores how much remains hidden in microbiology.

Source:

https://www.science.org/doi/10.1126/science.aed1656