Biology subjects

Carlson, N. A.

Publications and source records attributed to Carlson, N. A..

2 recordsLinked to original sources

bioRxiv2026

Helicase family proteins promote antiviral ADP-ribosylation of DNA purines

DarTG defense systems studied to date contain a DarT1 or DarT2 toxin that blocks phage replication by ADP-ribosylating DNA and a NADAR or macrodomain antitoxin, DarG, that reverses this modification at homeostasis. Here, we identify additional DarTG subfamilies, one of which comprises a DarT3 toxin, an ADP-ribosylhydrolase (ARH)-domain antitoxin, and a helicase family protein, DarH. The Escherichia coli DarHTG3 system confers broad phage defense, requires DarH and, unlike previously characterized DarTG systems, modifies adenine. Characterization of additional DarH-containing DarTG systems reveals that a subset also target guanine. Our data support a model in which ADP-bound DarH functions as a processivity factor by recruiting DarT to its single-stranded DNA substrate and allowing for ADP-ribosylation of multiple target sites. These findings reveal how a helicase family protein regulates an antiviral effector by promoting DNA engagement rather than unwinding and thereby expanding the functional repertoire of helicase family proteins in bacterial immunity.

microbiology↗

bioRxiv2024

Phages carry orphan antitoxin-like enzymes to neutralize the DarTG1 toxin-antitoxin defense system

The astounding number of anti-phage defenses encoded by bacteria is countered by an elaborate set of phage counter-defenses, though their evolutionary origins are often unknown. Here, we discover an orphan antitoxin counter-defense element in T4-like phages that can overcome the bacterial toxin-antitoxin phage defense system, DarTG1. The DarT1 toxin, an ADP-ribosyltransferase, modifies phage DNA to prevent replication while its cognate antitoxin, DarG1, is an ADP-ribosylglycohydrolase that reverses these modifications in uninfected bacteria. The orphan phage DarG1-like protein, which we term anti-DarT factor NADAR (AdfN), removes ADP-ribose modifications from phage DNA during infection thereby enabling replication in DarTG1-containing bacteria. AdfN, like DarG1, is in the NADAR superfamily of ADP-ribosylglycohydrolases found across domains of life. We find divergent NADAR proteins in unrelated phages that likewise exhibit anti-DarTG1 activity, underscoring the importance of ADP-ribosylation in bacterial-phage interactions, and revealing the function of a substantial subset of the NADAR superfamily.

microbiology↗