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

Autor(es)

Magalhaes, Yuli T. ^[1] ; Farias, Jessica O. ^[1] ; Silva, Luiz E. ^[1] ; Forti, Fabio L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Lab Biomol Syst Signaling, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DNA Repair; v. 100, APR 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/01753-6 - Identificação e investigação funcional de proteínas que interagem com as enzimas Cdc42 e DUSP12 em células humanas sob condições de instabilidade genômica: uma abordagem proteômica
• Beneficiário: Deborah Schechtman
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/16491-4 - Avaliação das proteínas VHR e NPM no reparo de DNA e proliferação de células leucêmicas
• Beneficiário: Jessica Oliveira Farias
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/03983-0 - Investigação molecular e funcional da interação de DUSP3 com proteínas nucleares: implicações em mecanismos de reparo de DNA
• Beneficiário: Fábio Luis Forti
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/01451-7 - Estudos da via de sinalização da GTPase Rho nas respostas de gliomas frente a estresse genotóxico
• Beneficiário: Yuli Thamires Magalhães
• Linha de fomento: Bolsas no Brasil - Doutorado Direto