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Modulation of RhoA GTPase activity sensitizes human cervix carcinoma cells to gamma-radiation by attenuating DNA repair pathways

Grant number: 15/18341-4
Support type:Regular Research Grants - Publications - Scientific article
Duration: October 01, 2015 - March 31, 2016
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Fábio Luis Forti
Grantee:Fábio Luis Forti
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Radiotherapy with gamma-radiation is widely used in cancer treatment to induce DNA damage reducing cell proliferation and to kill tumor cells. Although RhoA GTPase overexpression/hyperactivation is observed in many malignancies, the effect of RhoA activity modulation on cancer radiosensitivity has not been previously investigated. Here we generated stable HeLa cell clones expressing either the dominant negative RhoA-N19 or the constitutively active RhoA-V14 and compared the responses of these cell lines with that of parental HeLa cells, after treatment with low doses of gamma-radiation. HeLa-RhoA-N19 and HeLa-RhoA-V14 clones displayed reduced proliferation and survival compared to parental cells after radiation, and became arrested at cell cycle stages correlated with increased cellular senescence and apoptosis. Also, Chk1/2 and histone H2AX phosphorylation data, as well as comet assays, suggest that the levels of DNA damage and DNA repair activation and efficiency in HeLa cell lines are correlated with active RhoA. In agreement with these results, RhoA inhibition by C3 toxin expression drastically affected homologous recombination (HR) and non-homologous end joining (NHEJ). These data suggest that modulation of RhoA GTPase activity impairs DNA damage repair, increasing HeLa cell radiosensitivity. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OSAKI, JULIANA H.; ESPINHA, GISELE; MAGALHAES, YULI T.; FORTI, FABIO L. Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to gamma-Radiation by Attenuating DNA Repair Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016. Web of Science Citations: 1.

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