Bacterial enzyme makes DNA without template

Stanford University researchers reported in Science on April 17 that a bacterial antiviral system can make DNA in a way biologists do not usually expect: one strand is built without copying DNA or RNA. The work centers on DRT3, a defense-associated reverse transcriptase system found in bacteria that helps block phage infection. In lab tests, the system produced long double-stranded DNA with an alternating GT/AC pattern. The paper says one enzyme followed an RNA guide, while the other used a protein-based mechanism instead. ### How can DNA be made if there is no DNA or RNA template? The Science paper says DRT3 is made of two reverse transcriptases, Drt3a and Drt3b, plus a noncoding RNA. Drt3a makes the poly(GT) strand by reading a conserved ACACAC sequence embedded in that RNA, which fits the usual template-directed logic of nucleic-acid synthesis. Drt3b is the unusual part. The authors wrote that it synthesizes the matching poly(AC) strand “in the complete absence of a nucleic acid template,” and that conserved residues in Drt3b enforce the alternating base pattern. (science.org) The paper describes that as a protein-templated mechanism for sequence-specific DNA synthesis. ### What exactly did the researchers find this system makes? (science.org) The Stanford team reported that DRT3 synthesizes alternating poly(GT/AC) double-stranded DNA. In practical terms, that means the product is repetitive DNA with a defined two-base pattern rather than a random chain. Cryo-electron microscopy structures at 2.6 angstrom resolution showed what the paper called a D3-symmetric 6:6:6 complex of Drt3a, Drt3b and the noncoding RNA. (science.org) The structural result is part of the evidence the authors used to argue that Drt3b was not reading a hidden nucleic-acid template at its active site. ### Where does this fit in bacterial virus defense? The Phys.org summary of the study said the researchers introduced DRT3 into E. coli and challenged the bacteria with phages. (science.org) In those experiments, the system blocked infection and was activated by ST61, a phage-encoded protein, according to that report. The Science paper places DRT3 inside a broader group of defense-associated reverse transcriptases, or DRTs, that bacteria use against phages. (science.org) The authors note that other DRT systems already showed unusual behavior — including protein-primed nucleotide addition and production of long cDNA products — but said it had remained unclear whether bacteria could make sequence-specific DNA without a nucleic-acid template. (phys.org) ### Does this overturn the standard rule for DNA copying? The paper does not say ordinary genome replication works this way. The authors instead describe DRT3 as an additional mechanism within the “functional landscape” of nucleic-acid polymerases, not a replacement for the standard template-directed model used in cells. Science’s own framing and outside coverage focused on that distinction. (science.org) The novelty is that a bacterial defense enzyme appears able to generate a defined DNA sequence using features of the protein itself to control which base is added next. ### Who did the work, and where can readers find it? Pujuan Deng, Hyunbin Lee and Carlo Armijo are listed as co-first authors on the Science paper, and Alex Gao of Stanford University is the corresponding author. (science.org) The article is titled “Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase.” Science published the paper in 2026, and the study is available through the journal’s article and reader pages. (science.org) The next concrete step for readers is the full paper itself, which includes the structural analysis, biochemical assays and author list behind the April 17 report.