Protein builds DNA without template

Stanford researchers reported on April 16 in *Science* that a bacterial enzyme complex can build part of a DNA molecule without copying any DNA or RNA template, describing what the paper called a protein-templated mechanism for sequence-specific DNA synthesis. The study, led by Pujuan Deng, Hyunbin Lee, Carlo Armijo, Haoqing Wang and Alex Gao, examined a bacterial anti-phage system known as DRT3. The authors said one component, Drt3b, synthesized a complementary DNA strand “in the complete absence of a nucleic acid template.” The paper did not say cells generally replace template-based DNA replication with this pathway. Instead, the authors described DRT3 as part of a bacterial defense system against viruses, adding another example of unusual chemistry used by defense-associated reverse transcriptases. *Science* published the work under the title “Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase.” (science.org) ### What exactly did the researchers find? DRT3 consists of two reverse transcriptases, Drt3a and Drt3b, plus a noncoding RNA, the paper said. Together, the system synthesizes alternating poly(GT/AC) double-stranded DNA. The authors reported that Drt3a makes the poly(GT) strand from a conserved ACACAC sequence in the RNA, while Drt3b makes the complementary poly(AC) strand without a nucleic acid template. (science.org) The central claim is narrower than “DNA from nothing.” The paper described a repeat DNA product with a defined alternating pattern, not open-ended genome writing. Stanford’s biochemistry department summarized the result as a reverse transcriptase that creates sequence-specific DNA repeats using its own amino acids as the template. ### How can a protein act as a blueprint? (science.org) The *Science* abstract said conserved active-site residues in Drt3b enforce precise base alternation during synthesis. The authors wrote that Drt3b is protein-primed and that the enzyme’s own structure directs production of the poly(AC) strand. That is the basis for the paper’s description of a protein-templated mechanism. (science.org) The structural evidence came from cryo-electron microscopy at 2.6 angstrom resolution. The paper said those data revealed a D3-symmetric 6:6:6 complex made of Drt3a, Drt3b and the noncoding RNA. ### Does this overturn the usual rule that DNA copies a template? The authors placed the finding inside a broader enzyme landscape rather than presenting it as a replacement for standard replication. (science.org) The paper said nucleic acid polymerases are usually either template-directed or template-independent, and that known template-independent products are generally simple homopolymers, near-random tails or short motifs. The DRT3 result, they wrote, expands the functional landscape of nucleic acid polymerases by showing a protein-templated route to sequence-specific DNA synthesis. That wording matters. The study describes an additional mechanism in a specialized bacterial defense context, not a revision of how most organisms copy chromosomes. ### Where does this fit in bacterial virus defense? Defense-associated reverse transcriptases are widespread bacterial anti-phage systems, the paper said. The authors listed other DRT families with unusual activities, including AbiK, DRT9 and DRT2, and presented DRT3 as another antiviral pathway with distinct chemistry. (science.org) Stanford identified Alex Gao as the corresponding author, and PubMed lists the article as online ahead of print on April 16, 2026, with DOI 10.1126/science.aed1656. (science.org) Those records provide the clearest next step for readers looking for the primary source and named participants behind the work. (pubmed-d.ncbi.nlm.nih.gov)