Reveal new bacterial DNA process
- Stanford researchers reported in *Science* that a bacterial antiviral system called DRT3 makes repetitive double-stranded DNA with two reverse transcriptases and a noncoding RNA, including one strand made without a nucleic-acid template. - The team found DRT3 builds alternating poly(GT/AC) DNA, and cryo-electron microscopy at 2.6 angstroms showed a 6:6:6 complex of Drt3a, Drt3b, and RNA that organizes the reaction. - The work adds a new route for sequence-specific DNA synthesis to a fast-growing catalog of bacterial phage defenses. (science.org)
Most DNA-copying enzymes read an existing DNA or RNA template. A bacterial antiviral system described in *Science* can build one DNA strand without using a nucleic-acid template at all. (science.org) The system is called DRT3, short for defense-associated reverse transcriptase type 3. It is part of the anti-phage arsenal bacteria use against bacteriophages, the viruses that infect bacteria. (science.org) (nature.com) Reverse transcriptases usually copy RNA into DNA. In DRT3, the Stanford team found two reverse transcriptases, Drt3a and Drt3b, working with a noncoding RNA to make alternating poly(GT/AC) double-stranded DNA repeats. (science.org) One enzyme, Drt3a, makes the poly(GT) strand by reading a conserved ACACAC sequence in the noncoding RNA. The other, Drt3b, makes the matching poly(AC) strand in the absence of any nucleic-acid template, according to the paper. (science.org) The researchers used cryo-electron microscopy to solve the structure at 2.6 angstrom resolution. They reported a D3-symmetric complex containing six copies each of Drt3a, Drt3b, and the RNA scaffold. (science.org) That matters because nucleic-acid polymerases are usually sorted into two buckets: template-directed enzymes that copy a sequence, and template-independent enzymes that add simpler runs of bases. DRT3 does something in between by producing a defined alternating repeat through a protein-guided mechanism. (science.org) The paper lands amid a run of studies showing that bacterial reverse transcriptases do more than copy genetic material. A 2024 *Science* paper showed a different defense system, DRT2, can assemble long repetitive DNA that becomes a toxic repetitive gene during phage infection. (science.org 1) (science.org 2) In that earlier DRT2 work, phage infection triggered production of DNA with head-to-head 120-base-pair repeats that could extend for thousands of base pairs. The resulting repetitive RNA encoded a toxic repetitive protein that pushed cells into dormancy and blocked viral spread. (science.org) The new DRT3 study does not say all repetitive DNA comes from this pathway. It does show that bacteria carry at least one protein-based route to make sequence-specific DNA repeats as part of antiviral defense. (science.org) The authors were Pujuan Deng, Hyunbin Lee, Carlo Armijo, Haoqing Wang, and Alex Gao at Stanford. Their result widens the list of ways cells can write DNA when viruses attack. (science.org) (stanford.edu)
