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Id: lil-624020
Autor: Scher, Ricardo; Garcia, Juliana Bório Ferreira; Pascoalino, Bruno; Schenkman, Sergio; Cruz, Angela Kaysel.
Título: Characterization of anti-silencing factor 1 in Leishmania major
Fonte: Mem. Inst. Oswaldo Cruz;107(3):377-386, May 2012. ilus, graf, tab.
Idioma: en.
Projeto: FAPESP; . CAPES.
Resumo: Anti-silencing factor 1 (ASF1) is a histone chaperone that contributes to the histone deposition during nucleosome assembly in newly replicated DNA. It is involved in chromatin disassembly, transcription activation and in the cellular response to DNA damage. In Leishmania major the ASF1 gene (LmASF1) is located in chromosome 20 and codes for a protein showing 67% of identity with the Trypanosoma brucei TbASF1a. Compared to orthologous proteins, LmASF1 conserves the main residues relevant for its various biological functions. To study ASF1 in Leishmania we generated a mutant overexpressing LmASF1 in L. major. We observed that the excess of LmASF1 impaired promastigotes growth rates and had no impact on cell cycle progress. Differently from yeast, ASF1 overproduction in Leishmania did not affect expression levels of genes located on telomeres, but led to an upregulation of proteins involved in chromatin remodelling and physiological stress, such as heat shock proteins, oxidoreductase activity and proteolysis. In addition, we observed that LmASF1 mutant is more susceptible to the DNA damaging agent, methyl methane sulphonate, than the control line. Therefore, our study suggests that ASF1 from Leishmania pertains to the chromatin remodelling machinery of the parasite and acts on its response to DNA damage.
Descritores: Proteínas de Ciclo Celular/genética
Dano ao DNA/genética
Chaperonas de Histonas/fisiologia
Leishmania major/química
Mutação/genética
Proteínas de Protozoários/fisiologia
-Western Blotting
Eletroforese em Gel Bidimensional
Citometria de Fluxo
Cromatografia Gasosa-Espectrometria de Massas
Chaperonas de Histonas/genética
Proteínas de Protozoários/genética
Reação em Cadeia da Polimerase em Tempo Real
Limites: Animais
Coelhos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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