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During the <jats:italic>T. cruzi<\/jats:italic> infection, we demonstrated modulations in the host RNA polymerase II activity with the downregulation of ribonucleoproteins affecting host transcription and splicing machinery. These alterations could be a result of the initial damage to the host DNA caused by the presence of the parasite, however, the mechanisms are not well understood. Herein, we examined whether infection by <jats:italic>T. cruzi<\/jats:italic> coincided with enhanced DNA damage in the host cell. We studied the engagement of the DNA damage response (DDR) pathways at the different time points (0\u201324\u00a0h post-infection, hpi) by <jats:italic>T. cruzi<\/jats:italic> in LLC-MK2 cells. In response to double-strand breaks (DSB), maximum phosphorylation of the histone variant H2AX is observed at 2hpi and promotes recruitment of the DDR p53-binding protein (53BP1). During <jats:italic>T. cruzi<\/jats:italic> infection, Ataxia-telangiectasia mutated protein (ATM) and DNA-PK protein kinases remained active in a time-dependent manner and played roles in regulating the host response to DSB. The host DNA lesions caused by the infection are likely orchestrated by the non-homologous end joining (NHEJ) pathway to maintain the host genome integrity.<\/jats:p>","DOI":"10.1038\/s41598-024-53589-w","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T03:02:19Z","timestamp":1709521339000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells"],"prefix":"10.1038","volume":"14","author":[{"given":"Raul Alexander","family":"Gonz\u00e1les-C\u00f3rdova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thamires Rossi","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Gachet-Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnathan","family":"Andrade Vieira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lays Adrianne Mendon\u00e7a","family":"Trajano-Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elza Tiemi","family":"Sakamoto-Hojo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munira Muhammad Abdel","family":"Baqui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"53589_CR1","doi-asserted-by":"crossref","unstructured":"Chagas, C. 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