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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection

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Santos, Juliana C. [1, 2] ; Gambeloni, Rafael Z. [2] ; Roque, Aline T. [2] ; Oeck, Sebastian [3, 4] ; Ribeiro, Marcelo L. [2]
Total Authors: 5
[1] State Univ Campinas UNICAMP, Womens Hlth Hosp Prof Dr Jose Aristodemo Pinotti, Campinas, SP - Brazil
[2] Sao Francisco Univ, Med Sch, Clin Pharmacol & Gastroenterol Unit, Av Sao Francisco de Assis 218, BR-12916900 Braganca Paulista, SP - Brazil
[3] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 - USA
[4] Univ Duisburg Essen, Med Sch, Inst Cell Biol Canc Res, Essen - Germany
Total Affiliations: 4
Document type: Journal article
Source: American Journal of Pathology; v. 188, n. 2, p. 329-335, FEB 2018.
Web of Science Citations: 1

Gastric cancer (GC) is the second Leading cause of cancer-related mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes. Among other risk factors, Helicobacter pylori infection is considered the main driving factor of GC development. H. pylori infection increases DNA damage levels and leads to epigenetic dysregulation, which may favor gastric carcinogenesis. An early step in double-strand break repair is the recruitment of ataxia-telangiectasia mutated serine/threonine kinase (ATM) to the damaged site, where it plays a key role in advancing the DNA damage checkpoint process. H. pylori infection has been associated with the introduction of double-strand breaks in epithelial cells, triggering damage signaling and repair response involving ATM. Thus, the current study analyzed the effect of H. pylori infection on the DNA damage response sensor, ATM, in gastric epithelial cells and in biopsy specimens from patients with GC. In this study, we identified that H. pylori infection stimulated DNA damage, and therefore induced ATM in a virulence factor-dependent manner. In addition, we found that H. pylori might activate ATM through histone H3 and H4 hyperacetylation and DNA promoter hypomethylation. Our findings show a mechanism associating ATM signaling induction with H. pylori infection. (AU)

FAPESP's process: 15/08775-7 - Role of H. pylori infection on modulation of miRNAs associated with Wnt/b-catenin pathway
Grantee:Rafael Zuppardo Gambeloni
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 11/21710-0 - Analysis of epigenetic profile related with DNA repair systems influenced by H. pylori infection
Grantee:Juliana Carvalho Santos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/11862-6 - Evaluation of the regulatory role of genes associated with the via Wnt/b-catenin on the mechanisms of the DNA repair modulated by H. pylori
Grantee:Marcelo Lima Ribeiro
Support type: Regular Research Grants
FAPESP's process: 15/17768-4 - Evaluation of the regulatory role of b-catenin on MMR genes modulated by H. pylori
Grantee:Aline Tengan Roque
Support type: Scholarships in Brazil - Scientific Initiation