Leishmania major and Trypanosoma cruzi present distinct DNA damage responses

Autor(es)

Garcia, Juliana B. F. ^[1] ; Vieira da Rocha, Joao P. ^[2] ; Costa-Silva, Hellida M. ^[2] ; Alves, Ceres L. ^[2] ; Machado, Carlos R. ^[2] ; Cruz, Angela K. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ave Bandeirantes 3900, BR-14049904 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Ave Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Biochemical Parasitology; v. 207, n. 1, p. 23-32, MAY 2016.
• Citações Web of Science: 2

Resumo

Leishmania major and Trypanosoma cruzi are medically relevant parasites and interesting model organisms, as they present unique biological processes. Despite increasing data regarding the mechanisms of gene expression regulation, there is little information on how the DNA damage response (DDR) occurs in trypanosomatids. We found that L. major presented a higher radiosensitivity than T. cruzi. L major showed G1 arrest and displayed high mortality in response to ionizing radiation as a result of the inefficient repair of double-strand breaks (DSBs). Conversely, T. cruzi exhibited arrest in the S/G2 cell cycle phase, was able to efficiently repair DSBs and did not display high rates of cell death after exposure to gamma irradiation. L major showed higher resistance to alkylating DNA damage, and only L. major was able to promote DNA repair and growth recovery in the presence of MMS. ASF1c overexpression did not interfere with the efficiency of DNA repair in either of the parasites but did accentuate the DNA damage checkpoint response, thereby delaying cell fate after damage. The observed differences in the DNA damage responses of T. cruzi and L major may originate from the distinct preferred routes of genetic plasticity of the two parasites, i.e., DNA recombination versus amplification. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 10/20597-3 - Investigação da interação parasito-hospedeiro: explorando modelos de estudo de virulência e tropismo
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/50219-9 - Investigação sobre fatores e mecanismos do controle de expressão gênica em Leishmania: do papel de modificações pós-traducionais, RNAs não codificadores, cis-elementos e amplificação gênica
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/51854-1 - Caracterizacao dos possiveis mecanismos de acao de asf1 (anti silencing factor 1) em leishmania major
• Beneficiário: Juliana Bório Ferreira Garcia
• Modalidade de apoio: Bolsas no Brasil - Doutorado