Helicase family proteins promote antiviral ADP-ribosylation of DNA purines
- 1Washington University in St Louis School of Medicine
Abstract
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.
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BibTeX
@misc{griesman2026helicase,
title = {{Helicase family proteins promote antiviral ADP-ribosylation of DNA purines}},
author = {T. Griesman and A. Q. Arifah and E. J. Tomko and Y. Tan and N. Tsao and J. T. Trotter and S. S. Khochare and N. A. Carlson and N. Mosammaparast and D. Zhang and E. A. Galburt and C. Patinios and M. LeRoux},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763693},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763693v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Helicase family proteins promote antiviral ADP-ribosylation of DNA purines
AU - T. Griesman
AU - A. Q. Arifah
AU - E. J. Tomko
AU - Y. Tan
AU - N. Tsao
AU - J. T. Trotter
AU - S. S. Khochare
AU - N. A. Carlson
AU - N. Mosammaparast
AU - D. Zhang
AU - E. A. Galburt
AU - C. Patinios
AU - M. LeRoux
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763693
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763693v1
AB - 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.
ER -