How a Simple Defense Mechanism in Bacteria Broke the Conventions of DNA Synthesis

Over the past few decades, all our biology textbooks stated that DNA and RNA can only be replicated via enzymes that use a single strand of DNA or RNA as a template for replication,but scientists from Stanford, America have found a groundbreaking discovery in a simple defense mechanism in Escherichia coli that breaks this fundamental rule that we have grown up with.

The defense mechanism, DRT3 is used to defend bacteria against their natural predators, bacteriophages – viruses that break into bacteria and destroy them from the inside out.

Usually, DNA is copied from a template strand as one enzyme unzips the double helix and another enzyme, polymerase assembles nucleotides to create the DNA strand copy. However, the DRT3 system possesses an enzyme, DRT3b that can go around this rule and create repetitive DNA sequences without a nucleic acid template as it uses itself as a guide. DRT3 is made up of only 3 parts: two reverse-transcriptase enzymes, Drt3a and Drt3b, together with a non-coding RNA—an RNA molecule that isn’t translated into protein. DRT3a is a reverse transcriptase enzyme that synthesizes a specific, single strand of DNA and acts as a conventional RNA-templated polymerase by reading an embedded sequence in the non-coding RNA to produce DNA long-poly DNA repeats.

Chemists and biologists believe that further investigation of the enzyme Drt3b could reveal ways to make novel DNA sequences – completely new, artificially engineered, or previously undiscovered genetic codes that do not exist naturally; sequences that could help to produce DNA hydrogels to aid in tissue regeneration and drug delivery. The enzyme Drt3b, showed something that changes how the scientific community at large views of how life is able to create DNA and RNA sequences, the Drt3b enzyme carries amino acids in its active site where substrate molecules would usually be present for chemical reactions. These amino acids function like an RNA template to synthesise a DNA strand and the protein structure becomes the DNA blueprint in place of a DNA strand. More shockingly, the fact that the Drt3 system is found in various bacteria and not just E.coli, this new discovery may not be a rare exception but rather a common process.

CRISPR technology was also adapted from a bacterial defense system like Drt3b but Drt3b possesses potential for mindblowing discovery just as great if not greater than that of CRISPR technology. Drt3, as a bacterial system possessing reverse transcriptases, presents itself as a key player in some CRISPR bacterial defense systems as well as generating unique bacterial genes and reverse transcriptases are known for their possible functions that go beyond DNA replication.

How the Drt3 system works to protect bacteria against bacteriophage viruses is currently unknown but it is hypothesised that DNA helices made by Drt3b may act as ‘molecular sponges’ to absorb phage components to prevent their growth and reproduction or by enabling other bacterial immune responses. This could mean that Drt3 could be related to other discoveries relating to polymerase like proteins in other bacterial defense systems that also produce nucleic acid polymers for the inhibition and detection of bacteriophages.

This discovery in Drt3 and its Drt3b enzymes that broke the central dogma regarding DNA and protein formation sheds light on how microbial biology still remains a vast topic to be covered and with numerous bacterial systems still left uncharacterised, there is still huge scope for more breakthroughs in microbial biology and science as a whole.

Bibliography:

1. https://www.science.org/doi/10.1126/science.aed1656
2. https://www.sciencealert.com/dna-can-be-built-in-a-way-weve-never-seen-before-study-finds
3. https://www.dongascience.com/en/news/77445
4. https://www.science.org/content/article/scientists-stunned-fundamentally-new-way-life-produces-dna
5. https://pubmed.ncbi.nlm.nih.gov/41990131/
6. https://www.popularmechanics.com/science/health/a71109879/new-way-dna/