Leishmania major and Trypanosoma cruzi present distinct DNA damage responses

• Published in: Molecular and biochemical parasitology Vol. 207; no. 1; pp. 23 - 32
• Main Authors: Garcia, Juliana B.F., Rocha, João P.Vieira da, Costa-Silva, Héllida M., Alves, Ceres L., Machado, Carlos R., Cruz, Angela K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: Alkylating Agents - pharmacology; Anti-silencing factor 1; Cell Cycle Checkpoints - genetics; Cell Cycle Checkpoints - radiation effects; DNA Breaks, Double-Stranded - drug effects; DNA Breaks, Double-Stranded - radiation effects; DNA Damage - drug effects; DNA Damage - radiation effects; DNA damage response; DNA Repair; Gamma irradiation; Gamma Rays; Gene Expression; Leishmania major; Leishmania major - drug effects; Leishmania major - genetics; Leishmania major - metabolism; Leishmania major - radiation effects; Methyl methanesulfonate; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - genetics; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - radiation effects; Anti-silencing factor 1; Gamma irradiation; Methyl methanesulfonate; DNA damage response; Leishmania major; Trypanosoma cruzi
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2016.05.004

[Display omitted] •T. cruzi efficiently repair double-strand breaks in DNA.•L. major presents higher radiosensitivity than T. cruzi.•L. major exhibits higher resistance to alkylating DNA damage.•Overexpression of ASF1c in both parasites delayed cell fate after damage induction. 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.