Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

RHOAming Through the Nucleotide Excision Repair Pathway as a Mechanism of Cellular Response Against the Effects of UV Radiation

Full text
Author(s):
Magalhaes, Yuli T. [1] ; Silva, Gisele E. T. [1] ; Osaki, Juliana H. [1] ; Rocha, Clarissa R. R. [2] ; Forti, Fabio L. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Biomol Syst Signaling Lab, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, DNA Repair Lab, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY; v. 8, AUG 19 2020.
Web of Science Citations: 0
Abstract

Typical Rho GTPases include the enzymes RhoA, Rac1, and Cdc42 that act as molecular switches to regulate essential cellular processes in eukaryotic cells such as actomyosin dynamics, cell cycle, adhesion, death and differentiation. Recently, it has been shown that different conditions modulate the activity of these enzymes, but their functions still need to be better understood. Here we examine the interplay between RhoA and the NER (Nucleotide Excision Repair) pathway in human cells exposed to UVA, UVB or UVC radiation. The results show high levels and accumulation of UV-induced DNA lesions (strand breaks and cyclobutane pyrimidine dimers, CPDs) in different cells with RhoA loss of function (LoF), either by stable overexpression of negative dominant RhoA (RhoA-N19 mutant), by inhibition with C3 toxin or by transient silencing with siRNA. Cells under RhoALoFshowed reduced levels of gamma H2AX, p-Chk1 (Ser345) and p-p53 (Ser15) that reflected causally in their accumulation in G1/S phases, in low survival rates and in reduced cell proliferation, also in accordance with the energy of applied UV light. Even NER-deficient cells (XPA, XPC) or DNA translesion synthesis (TLS)-deficient cells (XPV) showed substantial hypersensitivity to UV effects when previously submitted to RhoALoF. In contrast, analyses of apoptosis, necrosis, autophagy and senescence revealed that all cells displaying normal levels of active RhoA (RhoA-GTP) are more resistant to UV-promoted cell death. This work reaffirms the role of RhoA protein signaling in protecting cells from damage caused by UV radiation and demonstrates relevant communicating mechanisms between actin cytoskeleton and genomic stability. (AU)

FAPESP's process: 11/05822-3 - Investigation of VHR (DUSP3) protein tyrosine phosphatase in DNA damage response induced by ultraviolet light in human melanoma cell lines
Grantee:Alexsandro dos Santos
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 10/09453-0 - The role of Rho GTPases in DNA damage response induced by ionizing radiation type gamma
Grantee:Juliana Harumi Osaki
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/01753-6 - Identification and functional investigation of proteins that interact with Cdc42 and DUSP12 enzymes in human cells under conditions of genomic instability: a proteomic approach
Grantee:Fábio Luis Forti
Support Opportunities: Regular Research Grants
FAPESP's process: 15/03983-0 - Molecular and functional investigation of the interactions between DUSP3 with nuclear proteins and its implications in DNA repair mechanisms
Grantee:Fábio Luis Forti
Support Opportunities: Regular Research Grants
FAPESP's process: 10/20506-8 - Use of gene reporter luciferase to determine DNA repair activity in animals cells
Grantee:Clarissa Ribeiro Reily Rocha
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/01451-7 - Investigating Rho GTPases pathways in the response of glioma cell lines to genotoxic stress
Grantee:Yuli Thamires Magalhães
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)