Bacteria shown making DNA differently

- Stanford researchers reported in Science that a bacterial anti-phage system called DRT3 makes double-stranded DNA with one strand built without any nucleic-acid template. - The DRT3 complex contains Drt3a, Drt3b, and a noncoding RNA; cryo-electron microscopy at 2.6 angstroms showed Drt3b enforcing an alternating AC pattern. - The work extends earlier reports of unusual bacterial reverse transcriptases, including DRT2 and DRT9, into protein-templated DNA synthesis. (science.org)

DNA is usually copied from DNA or RNA, but Stanford researchers report a bacterial enzyme complex that builds one DNA strand without either template. (science.org) The study, published in *Science* in April 2026, examined a bacterial anti-phage system called DRT3, short for defense-associated reverse transcriptase 3. The complex includes two enzymes, Drt3a and Drt3b, plus a noncoding RNA. (science.org) In ordinary template-directed synthesis, enzymes read an existing nucleic-acid sequence like a stencil and add matching building blocks. In DRT3, Drt3a still follows that rule, using an ACACAC sequence in the RNA to make a poly(GT) DNA strand. (science.org) The surprise came from Drt3b, which made the matching poly(AC) strand without any nucleic-acid template at all. The authors say conserved residues in Drt3b’s active site force the enzyme to alternate adenine and cytosine in a fixed pattern. (science.org) Using cryo-electron microscopy at 2.6-angstrom resolution, the team reconstructed a D3-symmetric 6:6:6 assembly of Drt3a, Drt3b, and the RNA. That structure supported the idea that Drt3b’s protein shape, rather than a DNA or RNA guide, dictates the sequence it writes. (science.org) This is not bacteria replacing normal chromosome replication with a new universal system. The paper describes a specialized defense pathway that bacteria use against bacteriophages, the viruses that infect them. (science.org) That distinction matters because reverse transcriptases in bacteria have already been turning up as odd antiviral tools. A 2024 *Science* paper showed another system, DRT2, making circular DNA products that reconstitute a new gene during phage infection. (science.org) The new DRT3 result pushes that story further by showing two different writing modes in one machine: one RNA-templated and one protein-templated. The authors describe it as a new mechanism for sequence-specific DNA synthesis, not just random nucleotide addition. (science.org) The DNA product here is also narrow in scope: an alternating dinucleotide repeat, written as poly(GT/AC), rather than an arbitrary gene-sized sequence. That means the finding changes how biologists think about what polymerases can do, while leaving the standard rules for most DNA copying intact. (science.org) Researchers still do not know exactly how DRT3’s repeat DNA blocks phage infection inside bacterial cells. But the paper adds one more example of bacteria hiding unfamiliar molecular tools inside their virus-defense systems. (science.org)

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