Researchers discover protein builds DNA

Stanford University researchers reported on April 16 that a bacterial anti-phage system can build a defined DNA sequence without copying an existing DNA or RNA strand, according to a paper in Science. The work centers on DRT3, a bacterial defense-associated reverse transcriptase system cloned from *Escherichia coli*. The authors said one part of the system, an enzyme called Drt3b, synthesized a complementary DNA strand “in the complete absence of a nucleic acid template.” The finding was described in the paper as a protein-templated mechanism for sequence-specific DNA synthesis. ### Which protein did the researchers say was doing this? Pujuan Deng, Hyunbin Lee, Carlo Armijo, Haoqing Wang and Alex Gao identified DRT3 as a three-part complex made of two reverse transcriptases — Drt3a and Drt3b — plus a noncoding RNA. In the Science paper, the team said the system synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo-electron microscopy at 2.6 angstrom resolution showed a D3-symmetric 6:6:6 complex of Drt3a, Drt3b and the RNA component. (science.org) Alex Gao, a Stanford biochemist and the paper’s corresponding author, said the surprising part was Drt3b. “The protein itself serves as the blueprint for the DNA sequence,” Gao told Science, according to secondary coverage that quoted the interview. ### If there was no template, what was Drt3a doing? Drt3a was still using a conventional nucleic-acid guide. (science.org) The Science paper said Drt3a makes the poly(GT) strand from a conserved ACACAC template embedded in the noncoding RNA. That means the system is not wholly template-free: one strand is RNA-templated, while the matching strand is produced by Drt3b without a nucleic-acid template. (sciencealert.com) The paper said Drt3b then synthesizes the complementary poly(AC) strand in a protein-primed reaction. The authors wrote that conserved active-site residues specific to Drt3b enforce the alternating base pattern. ### What exactly did the paper claim was new? Science published the paper as “Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase.” The authors said nucleic-acid polymerases are generally understood to fall into two groups: template-directed enzymes that copy an existing sequence, and template-independent enzymes that usually make low-complexity or short products. (science.org) They wrote that their results “expand the functional landscape of nucleic acid polymerases” by showing a protein-templated route to sequence-specific DNA synthesis. The Gao lab’s publications page lists the paper as a 2026 Science article and says it was highlighted in Science News. The Science metadata shown in search results lists the article as published on April 16, 2026. ### Does this mean biology textbooks were wrong about DNA replication? The paper did not say standard DNA replication in cells works this way. The experiments described a bacterial anti-phage defense system, not the ordinary chromosome-copying machinery used across life. (science.org) The product reported was an alternating dinucleotide repeat DNA, poly(GT/AC), rather than a general-purpose genome-copying mechanism. (gaolab.bio) ScienceAlert, citing Gao’s comments to Science, said the finding adds a new mechanism rather than replacing the standard account of how DNA is usually copied. That interpretation is consistent with the paper’s narrower claim about “expanding” known polymerase functions. ### What is this system supposed to do in bacteria? (science.org) The Science paper described DRTs as widespread bacterial anti-phage systems that use unconventional polynucleotide synthesis. In this case, DRT3 was studied as part of bacterial defense against viruses that infect bacteria. The authors did not settle exactly how the DNA product blocks phage infection. (sciencealert.com) A separate April 2026 bioRxiv preprint from researchers in Shenzhen reported another defense-associated reverse transcriptase, DRT7, that also makes protein-templated DNA during antiviral defense. That preprint has not been peer reviewed, but it points to similar questions about how such systems are triggered and how the DNA products act during phage attack. (science.org) ### Where can readers find the study and what comes next? Science published the peer-reviewed DRT3 study under DOI 10.1126/science.aed1656, with Alex Gao as corresponding author and Stanford University affiliations listed for the authors. The next concrete step is further work on mechanism: Gao said researchers do not yet know exactly how bacteria use DRT3 against phages. (science.org) (biorxiv.org)