“DNA replication seemed to hold no more surprises. For decades, textbooks have stated that new DNA is always generated along a template—either along the DNA itself (where the double strand opens up and is replicated into two more double strands) or along an RNA molecule.
However, it turns out there is another way. A study published in the journal *Science* now reveals that new DNA can be created without any nucleic acid template at all; instead, a DNA-synthesizing protein itself serves as the template.
In this instance, the amino acids mimic RNA, effectively turning the protein structure into a blueprint. This represents a previously unknown method of DNA production—comparable to a 3D printer that derives the design specifications for the objects it creates from its own components. This unusual process was discovered by a team led by Alex Gao at Stanford University in California.
What kind of protein is it that turns established dogmas regarding DNA synthesis on their head?
The protein is part of a molecular machine known by the cryptic name DRT3, which plays a role in the immune defense of the gut bacterium *Escherichia coli*.
This molecular machine consists of two proteins and an RNA molecule, with three copies of each component present.
The two proteins are reverse transcriptases—enzymes that generate a DNA strand from an RNA template; one is named Drt3a and the other Drt3b.
The RNA component of the machine is a poly(AC), consisting solely of repeating nucleotides containing the bases adenine and cytosine. Using this RNA as a guide, the reverse transcriptase Drt3a synthesizes DNA of complementary poly(GT) strand made of nucleotides containing the bases guanine and thymine.
However, the true star of this molecular machine is the second reverse transcriptase. Drt3b. It uses the amino acids in its active site to form a poly(AC) strand, which then pairs with the poly(GT) strand synthesized by the other reverse transcriptase to form a DNA double helix.
Because DRT3 is part of the *Escherichia coli* immune system, Alex Gao and his colleagues suspect that the resulting double helix plays a role in phage defense.
Phages are the natural enemies of bacteria; they are viruses that dock onto cells and inject their nucleic acids into the bacterial interior. Once inside, they either hijack the bacterium to produce phage components—which then self-assemble into new phages and exit the cell—or they integrate their genetic material into the bacterium's genome and lie low for the time being.
Gao and his colleagues hypothesize that the double strand synthesized by Drt3 acts like a molecular sponge or bubble wrap, either encapsulating and neutralizing phage components or marking them for the bacterial immune system, thereby making them vulnerable to attack.
Why is this discovery so interesting? Drt3b produces only a simple repetitive sequence, not a complex new set of genetic instructions. Gao and his colleagues do not view the protein's activity as a general mechanism for the sequence-specific synthesis of new DNA, either. Nevertheless, the researchers are electrified. It is the "all-in-one" aspect that fascinates them.
Through its structure alone, Drt3b possesses everything required for DNA synthesis—even if, for now, it is capable of producing only a simple sequence.
Speculation is turning toward its potential, as an unassuming tool from a bacterial immune system recently caused a sensation: the CRISPR/Cas9 gene-editing system. In record time, it was transformed into a programmable precision scalpel for targeted genome editing—a tool that has become indispensable in today’s laboratories.
What if Drt3b’s capabilities could also be elevated to a new level through targeted modifications? The value of a biological machine capable of synthesizing DNA based solely on its structure would be immense.” [1]
1. Der neue Weg zur Erbsubstanz: DNA lässt sich allein anhand ihrer Struktur synthetisieren. Frankfurter Allgemeine Zeitung; Frankfurt. 27 May 2026: N2. HILDEGARD KAULEN