Researchers make DNA inside bacteria

- Stanford researchers reported in Science that a bacterial anti-phage system called DRT3 makes new DNA inside cells using a protein-shaped template. - The DRT3 complex forms a 6:6:6 assembly and builds alternating poly(GT/AC) double-stranded DNA, with one enzyme guided by an ACACAC RNA segment. - The work adds a third route for DNA synthesis beyond standard copying and random addition. (science.org)

DNA is usually made by copying another DNA or RNA strand. A Science paper from Stanford reports a bacterial defense system that instead uses a protein structure to guide part of the sequence. (science.org) The system is called DRT3, short for defense-associated reverse transcriptase 3. It is one of the molecular tools bacteria use against bacteriophages, the viruses that infect bacteria. (science.org) (nature.com) Most polymerases work like copy machines: they read an existing nucleic-acid template and add matching letters. A smaller class can add letters without a template, but those products are usually low-information tails rather than a defined sequence. (science.org) The Stanford team found that DRT3 makes a very specific product: alternating poly(GT/AC) double-stranded DNA. In the structure they solved, DRT3 is built from Drt3a, Drt3b, and a noncoding RNA in a D3-symmetric 6:6:6 complex at 2.6-angstrom resolution. (science.org) One part still follows the familiar rule. Drt3a makes the poly(GT) strand using a conserved ACACAC segment in the noncoding RNA as its template. (science.org) The unusual step comes next. Drt3b synthesizes the matching poly(AC) strand without reading DNA or RNA, and the paper says the protein’s own shape acts as the guide for that sequence. (science.org) That means the system is not making arbitrary genomes from scratch. It is making a repeating dinucleotide pattern, but doing it through a route that does not fit the standard template-copying model for sequence-specific DNA synthesis. (science.org) (yahoo.com) Reverse transcriptases are best known from retroviruses, where they copy RNA into DNA. In bacteria, related enzymes have emerged as a large class of anti-phage systems, and recent studies have shown several defense-associated reverse transcriptases making unusual DNA products during infection. (science.org) (nature.com) That broader context matters for phage biology. Reviews in Nature note that bacteria carry a large and growing catalog of antiviral systems, and DRT3 adds another example of how those systems turn nucleic-acid chemistry into immunity. (nature.com) (science.org) The paper does not present this as a replacement for normal DNA replication. It shows that, in one bacterial defense pathway, sequence-defined DNA can be assembled through a protein-templated step inside a living cell. (science.org) The immediate next question is what that repeating DNA does during infection. For now, the study puts one concrete result on the table: bacteria have a way to write a specific DNA pattern that biology textbooks did not previously describe. (science.org)

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