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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.)

GTPases, genome, actin: A hidden story in DNA damage response and repair mechanisms

Full text
Author(s):
Magalhaes, Yuli T. [1] ; Farias, Jessica O. [1] ; Silva, Luiz E. [1] ; Forti, Fabio L. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Lab Biomol Syst Signaling, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: DNA Repair; v. 100, APR 2021.
Web of Science Citations: 0
Abstract

The classical small Rho GTPase (Rho, Rac, and Cdc42) protein family is mainly responsible for regulating cell motility and polarity, membrane trafficking, cell cycle control, and gene transcription. Cumulative recent evi-dence supports important roles for these proteins in the maintenance of genomic stability. Indeed, DNA damage response (DDR) and repair mechanisms are some of the prime biological processes that underlie several disease phenotypes, including genetic disorders, cancer, senescence, and premature aging. Many reports guided by different experimental approaches and molecular hypotheses have demonstrated that, to some extent, direct modulation of Rho GTPase activity, their downstream effectors, or actin cytoskeleton regulation contribute to these cellular events. Although much attention has been paid to this family in the context of canonical actin cytoskeleton remodeling, here we provide a contextualized review of the interplay between Rho GTPase signaling pathways and the DDR and DNA repair signaling components. Interesting questions yet to be addressed relate to the spatiotemporal dynamics of this collective response and whether it correlates with different sub-cellular pools of Rho GTPases. We highlight the direct and indirect targets, some of which still lack experimental validation data, likely associated with Rho GTPase activation that provides compelling evidence for further investigation in DNA damage-associated events and with potential therapeutic applications in translational medicine. (AU)

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: 17/16491-4 - Evaluation of VHR and NPM proteins in DNA repair and proliferation of leukemic cells
Grantee:Jessica Oliveira Farias
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
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: 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)