A bacterial enzyme can build a precise repeating DNA strand without reading a DNA or RNA template for that strand. Instead, amino acids positioned inside the enzyme determine which DNA building block is added next. Two structural studies of the DRT3 antiviral system reveal a previously undocumented mode of DNA synthesis—but not a general route for proteins to encode arbitrary genetic information.

Key facts

  • DRT3 is a bacterial defense system containing two reverse transcriptases and a non-coding RNA.
  • One enzyme copies an ACACAC RNA sequence to make a repeating GT DNA strand.
  • The second enzyme makes the complementary AC strand without a nucleic-acid template.
  • Cryo-electron microscopy showed protein side chains controlling the alternating nucleotide pattern.
  • The system makes one repetitive product; scientists have not shown that it can write arbitrary DNA sequences.

One DNA molecule, two radically different assembly lines

Most DNA polymerases work by reading an existing nucleic-acid strand. An A on one strand pairs with T on the other; C pairs with G. That complementary geometry allows a sequence to be copied with high fidelity.

The bacterial DRT3 system produces double-stranded DNA with an alternating GT/AC pattern, but its two strands are made differently. Drt3a behaves like a reverse transcriptase: it reads a short ACACAC sequence in a non-coding RNA and produces a repeating GT DNA strand.

Drt3b creates the complementary AC strand. Yet researchers found no DNA or RNA template entering the part of the enzyme where templating would ordinarily occur. The channel is physically blocked. Instead, conserved amino-acid side chains sit beside the active site and constrain the enzyme to alternate between cytosine and adenine nucleotides.

In effect, the protein’s three-dimensional structure supplies the pattern. The enzyme is both machine and limited template.

Cryo-electron microscopy exposed the molecular trick

Researchers used cryo-electron microscopy, a technique that reconstructs molecular structures from many images of rapidly frozen particles. One team resolved the DRT3 complex to 2.6 ångströms, fine enough to position important protein regions and nucleic-acid components.

The complex contains six copies each of Drt3a, Drt3b and the non-coding RNA. Structural and biochemical experiments showed that Drt3b begins the new DNA strand from a protein-linked starting point and then extends it without an opposing nucleic-acid template.

Independent work published in Cell reached the same central conclusion and identified active-site-adjacent residues that act as gates for alternating nucleotide addition. Converging structural results make the mechanism far stronger than an inference based only on the final DNA product.

Why would bacteria make repetitive DNA during an attack?

DRT stands for defense-associated reverse transcriptase. These systems help bacteria resist bacteriophages—the viruses that infect them. The repeating double-stranded DNA made by DRT3 appears to participate in an abortive-infection response.

In that strategy, an infected bacterium halts its own growth or dies before the virus can complete replication, protecting nearby members of the bacterial population. Experiments found that a phage protein called Gam, which inhibits the bacterial DNA-repair complex RecBCD, can trigger the DRT3 response.

The exact chain connecting the unusual DNA product to growth arrest still needs clarification. The study establishes how the DNA is made more firmly than what every downstream molecule does with it.

Does this overturn the central dogma?

No. The central dogma concerns the flow of sequence information among DNA, RNA and protein. DRT3 does not show a protein being read as a general genetic sequence and converted back into arbitrary DNA.

Its protein active site enforces one simple repeating AC pattern. There is no evidence that researchers can program Drt3b to write a gene, a paragraph of genetic instructions or even a wide range of short sequences.

The discovery does expand the known chemistry of polymerases. It shows that a protein surface can provide enough spatial information to select successive nucleotides in a defined pattern without an opposing nucleic-acid strand. That mechanism could eventually inspire new biotechnology, but programmability remains a research question rather than an available tool.

What scientists will ask next

Researchers now need to determine how broadly this mechanism occurs across bacteria, how the repeating DNA activates defense, and whether altering the templating residues can safely change the output sequence. They will also need to learn whether the system’s unusual chemistry can be separated from its natural self-destructive response.

For now, DRT3 is best understood as a highly specialized bacterial antiviral machine—and an elegant exception to the assumption that every precisely specified DNA strand requires a DNA or RNA template.

Sources

  1. Deng et al., “Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase,” Science (2026).
  2. Wang et al., “Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system,” Cell (2026).

Editorial disclosure: The lead image is a molecular concept illustration and is not an atomically exact rendering of DRT3. SciQuest received no payment to cover this research. To report a possible error, contact SciQuest.