Landon Getz (left) and Amy Qian (right)

27 August 2026

By Megan Fleming

A University of Toronto lab has discovered that one of biology’s oldest housekeeping enzymes has a hidden second job.

Every living cell — bacterial, viral, or human — carries a small group of repair enzymes called DNA glycosylases with a simple job. They patrol the genome for mistakes and fix them before they become permanent mutations. This maintenance work isn’t very glamorous.

So, it puzzled a research team led by Karen Maxwell, a professor in the department of biochemistry at U of T’s Temerty Faculty of Medicine and 2026 Peter Gilgan Canada Gairdner Momentum Award Laureate, when they found two of these totally average repair enzymes living a double life.

In a new paper published in Nature Microbiology, researchers have discovered that two ordinary repair enzymes – which they’ve named Dag1 and Dag2 – have a second, previously hidden function: fighting off bacteriophages (phages) or viruses that infect bacteria, and one of the oldest evolutionary rivalries in biology. You could call these repair enzymes the Hannah Montanas of microbiology: molecules with perfectly ordinary day jobs and hidden secret identities.

This discovery is based on the lab’s earlier work published in Nature Microbiology and previously covered by EPIC. We already know two mysterious proteins helped bacteria survive phage attacks, but it was unclear how.

“What are these proteins [DNA glycosylases] actually doing, at a biochemical level, to protect against these viruses?” asked Landon Getz, co-first author and a postdoctoral fellow in Karen Maxwell’s lab in the department of biochemistry at U of T’s Temerty Faculty of Medicine.

The team first confirmed that Dag1 and Dag2 were reacting to phages that put chemical modifications on their guanine bases — one of DNA’s four basic building blocks — to disguise themselves from the usual defences bacteria use.

When they tested phages without this modification, Dag1 and Dag2 left them alone. But phages carrying the modified guanine costume were reliably detected and destroyed.

That costume, however, isn’t always complete, which Amy Qian, co-first author and PhD candidate in the Maxwell Lab, helped unpack. Phages have fascinated Qian since she started her PhD — she often wears a small silver bacteriophage pendant. “Why would something so common in DNA repair, like a housekeeping, maintenance gene, be used by bacteria as an anti-phage defence gene?” she asked. “That’s kind of what really hooked me.”

“We found that some phages are 100% modified and some are maybe 20% modified,” said Qian, who is also a 2026 EPIC Doctoral Awardee. “And those 20% modified phages can mutate to lose the modification altogether so the defence system no longer has anything to target.”

The gene responsible for adding the guanine modification can mutate at random, and, when it does, the phage’s DNA emerges unmodified, invisible to Dag1 and Dag2 once more. But it’s a trade-off: without the camouflage, the phage may become exposed again to the bacterial defences it was trying to hide from in the first place.

With this mechanism established, Getz turned to a broader question: were Dag1 and Dag2 one-of-a-kind, or part of something bigger? Similar genes are normally searched by sequence. It’s the standard approach, but it can miss proteins that have changed too much at the genetic level to be recognized as related. So, Getz searched by protein structure instead, since even distantly related proteins tend to keep a similar three-dimensional shape long after their sequences diverge.

Getz’s search turned up a large, diverse family of related glycosylases scattered across many different bacteria, many of which the team tested directly and confirmed to be involved in antiphage defences. Maxwell commented: “It surprised me how many different families we found, and it allowed us to annotate the functions of tens of thousands of proteins in bacteria that nobody had any idea what they did. It isn’t just that we found them; it’s that they actually are all performing the same function.”

The search also turned up a second, unrelated family of repair enzymes that defends against phages using an entirely different disguise: modified thymidine, another of DNA’s building blocks, instead of guanine.

What started as two overlooked proteins turned out to be part of a much larger, previously invisible strategy. Beyond identifying Dag1 and Dag2 specifically, the approach itself is a big part of the story. Both enzymes were found within integrons or clusters of genes that bacteria can pick up from their environment, often functioning like a grab-bag of tools the bacterium can call on when needed, including, it turns out, an outsized share of anti-phage defences.

“I think the use that other researchers will get out of this is really showing that these integrons are full of defences, which we showed in our previous work, and then this one really proof-of-concepted this idea that we could use them to identify many, many more,” said Getz, who is also the founder of the Pride in Microbiology network.

That proof of concept has an immediate real-world application: phage therapy, the use of viruses to treat bacterial infections, is gaining ground as a promising alternative to antibiotics amid rising drug resistance.

“The more we identify how bacteria are defending themselves against phages, the better we’re able to engineer phages for the future that we can actually use in therapeutics,” said Getz.

EPIC has been part of this story at multiple career stages, starting with Maxwell herself, a longtime EPIC member whose lab’s collaborative environment helped this project grow from two curious proteins into a much bigger discovery.

Getz’s own path through this work was supported by a GSK EPIC Convergence Postdoctoral Fellowship in Antimicrobial Resistance, awarded during his time as a postdoctoral fellow in the Maxwell lab (the fellowship has since concluded).

Qian is a recent EPIC Doctoral Award recipient, whose grant funded her travel to present this work at the Symposium on the Immune System of Bacteria in New York in April 2026. The grant is also funding what’s coming next: her search for natural, phage-encoded ways to defeat these very defence systems.

She credits much of her growth as a scientist to mentorship. “Landon has been a really great mentor — he introduced me to this project on day one of my rotation,” she said. “In my first year, I had daily discussions with him. Those conversations were more valuable training than any single technique. It’s an untraditional kind of learning, just being in the space with other researchers, constantly discussing things with your mentor.”

An ancient, unglamorous repair enzyme turns out to have been living a double life all along, uncovered through a PI’s long-view instincts, a postdoc’s eye for structure, and a trainee’s willingness to chase a strange phenotype.”