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Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen Cryptococcus neoformans.
Oliveira, Rayssa Karla de Medeiros; Hurtado, Fabián Andrés; Gomes, Pedro Henrique; Puglia, Luiza Lassi; Ferreira, Fernanda Fonsêca; Ranjan, Kunal; Albuquerque, Patrícia; Poças-Fonseca, Márcio José; Silva-Pereira, Ildinete; Fernandes, Larissa.
Afiliação
  • Oliveira RKM; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Hurtado FA; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Gomes PH; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Puglia LL; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Ferreira FF; Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Ranjan K; Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Albuquerque P; Faculty of Ceilândia, University of Brasília, Brasília 72.220-275, Brazil.
  • Poças-Fonseca MJ; Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Silva-Pereira I; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70.910-900, Brazil.
  • Fernandes L; Faculty of Ceilândia, University of Brasília, Brasília 72.220-275, Brazil.
J Fungi (Basel) ; 7(2)2021 Feb 12.
Article em En | MEDLINE | ID: mdl-33673204
Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of Cryptococcus neoformans, a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals. We focused on the characterization of C. neoformansAPN1 and APN2 putative genes, aiming to evaluate a possible role of the predicted Apurinic/apyrimidinic (AP) endonucleases 1 and 2 of the base excision repair (BER) pathway on C. neoformans response to stress conditions and virulence. Our results demonstrated the involvement of the putative AP-endonucleases Apn1 and Apn2 in the cellular response to DNA damage induced by alkylation and by UV radiation, in melanin production, in tolerance to drugs and in virulence of C. neoformans in vivo. We also pointed out the potential use of DNA repair inhibitor methoxy-amine in combination with conventional antifungal drugs, for the development of new therapeutic approaches against this human fungal pathogen. This work provides new information about the DNA damage response of the highly important pathogenic fungus C. neoformans.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article