title: Leishmania major and Trypanosoma cruzi present distinct DNA damage responses.
abstract: 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.
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, 14049-904, Ribeirão Preto, SP, Brazil. Electronic address: julianaborio@yahoo.com.br.
authors.forename: Juliana B F
authors.initials: JB
authors.lastname: Garcia
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil. Electronic address: joaopvr@yahoo.com.br.
authors.forename: João P Vieira da
authors.initials: JP
authors.lastname: Rocha
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil. Electronic address: hellidamarina@yahoo.com.br.
authors.forename: Héllida M
authors.initials: HM
authors.lastname: Costa-Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil. Electronic address: ceres_luciana@yahoo.com.br.
authors.forename: Ceres L
authors.initials: CL
authors.lastname: Alves
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil. Electronic address: crmachad@icb.ufmg.br.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Machado
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, 14049-904, Ribeirão Preto, SP, Brazil. Electronic address: akcruz@fmrp.usp.br.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Cruz
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D005720:Gamma Rays; D015870:Gene Expression; D018320:Leishmania major / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects
chemical_list: D000477:Alkylating Agents; D018832:Molecular Chaperones
keywords: Anti-silencing factor 1; DNA damage response; Gamma irradiation; Leishmania major; Methyl methanesulfonate; Trypanosoma cruzi