All living cells are subject to agents that promote DNA damage. A particularly lethal lesion are interstrand crosslinks (ICL), a property exploited by several anti-cancer chemotherapies. In yeast and humans enzymes that play key roles in repairing such damage include the nucleases SNM1, MRE11, FAN1 and EXO1. In this project, we plan to evaluate the function of the homologues expressed by Trypanosoma cruzi, the causative agent of Chagas disease, with the aim of determining their role and importance to this parasite.
Sullivan, J.A., J.L. Tong, M. Wong, A. Kumar, H. Sarkar, S. Ali, I. Hussein, I. Zaman, E.L. Meredith, N.A. Helsby, L. Hu and S.R. Wilkinson (2015). Unravelling the role of SNM1 in the DNA repair system of Trypanosoma brucei. Molecular Microbiology 96, 827-838.
Wilkinson, S.R., C. Bot, J.M. Kelly, and B.S. Hall (2011). Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives. Current Topics in Medicinal Chemistry. 11, 2072-2084.
Wilkinson, S.R. and J.M. Kelly (2009). Trypanocidal drugs: mechanisms, resistance and new targets. Expert Reviews in Molecular Medicine. 11, e30.
Sengerová. B., A.T. Wang and P.J. McHugh (2011). Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair. Cell Cycle 10, 3999-4008
Genois, M.M., E.R. Paquet, M.C. Laffitte, R. Maity, A. Rodrigue, M. Ouellette and J.Y. Masson (2014). DNA repair pathways in trypanosomatids: from DNA repair to drug resistance. Microbiology and Molecular Biology Reviews. 78, 40-734.