The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress
Identifikátory výsledku
Kód výsledku v 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>
Nalezeny alternativní kódy
RIV/68378050:_____/20:00538129
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10600 - Biological sciences
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Nature Communications [online]
ISSN
2041-1723
e-ISSN
—
Svazek periodika
11
Číslo periodika v rámci svazku
1
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
16
Strana od-do
5117
Kód UT WoS článku
000581916500031
EID výsledku v databázi Scopus
2-s2.0-85092321840