The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F20%3A10440290" target="_blank" >RIV/00216208:11310/20:10440290 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/20:00538129
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aP-O3ZBemv" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aP-O3ZBemv</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-020-18857-z" target="_blank" >10.1038/s41467-020-18857-z</a>
Alternative languages
Result language
angličtina
Original language name
The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress
Original language description
Exposure of gastric epithelial cells to the bacterial carcinogen Helicobacter pylori causes DNA double strand breaks. Here, we show that H. pylori-induced DNA damage occurs co-transcriptionally in S-phase cells that activate NF-kappa B signaling upon innate immune recognition of the lipopolysaccharide biosynthetic intermediate beta -ADP-heptose by the ALPK1/TIFA signaling pathway. DNA damage depends on the bi-functional RfaE enzyme and the Cag pathogenicity island of H. pylori, is accompanied by replication fork stalling and can be observed also in primary cells derived from gastric organoids. Importantly, H. pylori-induced replication stress and DNA damage depend on the presence of co-transcriptional RNA/DNA hybrids (R-loops) that form in infected cells during S-phase as a consequence of beta -ADP-heptose/ ALPK1/TIFA/NF-kappa B signaling. H. pylori resides in close proximity to S-phase cells in the gastric mucosa of gastritis patients. Taken together, our results link bacterial infection and NF-kappa B-driven innate immune responses to R-loop-dependent replication stress and DNA damage. The bacterial pathogen Helicobacter pylori is known for its ability to induce DNA double-strand breaks in the genome of its target cells. Here, we show that H. pylori-induced DNA damage and replication stress occurs in S-phase cells as a result of R-loop-mediated transcription/replication conflicts that are triggered by activation of the ALPK1/TIFA/NF-kappa B signaling axis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications [online]
ISSN
2041-1723
e-ISSN
—
Volume of the periodical
11
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
5117
UT code for WoS article
000581916500031
EID of the result in the Scopus database
2-s2.0-85092321840