DUSP3 maintains genomic stability and cell proliferation through modulation of the NER pathway and cell cycle regulatory proteins

Autor(es)

Russo, Lilian Cristina ^[1] ; Farias, Jessica Oliveira ^[1] ; Forti, Fabio Luis ^[1]

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: CELL CYCLE; v. 19, n. 12 MAY 2020.
• Citações Web of Science: 0

Resumo

The DUSP3 phosphatase regulates cell cycle, proliferation, apoptosis and senescence of different cell types, lately shown as a mediator of DNA repair processes. This work evaluated the impact of DUSP3 loss of function (lof) on DNA repair-proficient fibroblasts (MRC-5), NER-deficient cell lines (XPA and XPC) and translesion DNA synthesis (TLS)-deficient cells (XPV), after UV-radiation stress. The levels of DNA strand breaks, CPDs and 6-4-PPs have accumulated over time in all cells under DUSP3 lof, with a significant increase in NER-deficient lines. The inefficient repair of these lesions increased sub-G1 population of XPA and XPC cells 24 hours after UV treatment, notably marked by DUSP3 lof, which is associated with a reduced cell population in G1, S and G2/M phases. It was also detected an increase in S and G2/M populations of XPV and MRC-5 cells after UV-radiation exposure, which was slightly attenuated by DUSP3 lof due to a discrete increase in sub-G1 cells. The cell cycle progression was accompanied by changes in the levels of the main Cyclins (A1, B1, D1 or E1), CDKs (1, 2, 4 or 6), and the p21 (Cip1) inhibitor, in a DUSP3-dependent manner. DUSP3 lof affected the proliferation of MRC-5 and XPA cells, with marked worsening of the XP phenotype after UV radiation. This work highlights the roles of DUSP3 in DNA repair fitness and in the fine control of regulatory proteins of cell cycle, essential mechanisms to maintenance of genomic stability. (AU)

• Processo FAPESP: 17/16491-4 - Avaliação das proteínas VHR e NPM no reparo de DNA e proliferação de células leucêmicas
• Beneficiário: Jessica Oliveira Farias
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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: Fábio Luis Forti
• Modalidade de apoio: Auxílio à Pesquisa - Regular