The ALPK1/TIFA/NF-kappa B axis links a bacterial carcinogen to R-loop-induced replication stress

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00538129" target="_blank" >RIV/68378050:_____/20:00538129 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/20:10440290

Result on the web

<a href="https://www.nature.com/articles/s41467-020-18857-z" target="_blank" >https://www.nature.com/articles/s41467-020-18857-z</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>

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 betaADP-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 betaADP-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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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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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

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