Leishmania major and Trypanosoma cruzi present distinct DNA damage responses

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Molecular and Biochemical Parasitology; v. 207, n. 1, p. 23-32, MAY 2016.
• Web of Science Citations: 2

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. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 10/20597-3 - Host-parasite interaction: models for studying virulence and tropism
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/50219-9 - Studying the control of gene expression in Leishmania: post-translational modification, non coding RNAs, cis-elements and gene amplification
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants