Characterization of anti-silencing factor 1 in Leishmania major

Autor(es)

Scher, Ricardo ^{[1, 2]} ; Ferreira Garcia, Juliana Borio ^[1] ; Pascoalino, Bruno ^[3] ; Schenkman, Sergio ^[3] ; Cruz, Angela Kaysel ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049904 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sergipe, Ctr Ciencias Biol & Saude, Dept Morfol, Aracaju, SE - Brazil

^[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Memórias do Instituto Oswaldo Cruz; v. 107, n. 3, p. 377+, MAY 2012.
• Citações Web of Science: 5

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. (AU)

• Processo FAPESP: 99/12403-3 - Do genoma à biologia de Leishmania: uma abordagem compreensiva
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/50323-7 - Estudo do controle da expressão gênica e plasticidade genética em Leishmania
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático