Fenoy Ignacio M, Bogado Silvina S, Contreras Susana M, Gottifredi Vanesa, Angel Sergio O
Laboratorio de Parasitología Molecular, IIB-INTECH, CONICET-UNSAM Chascomús, Argentina.
Cell Cycle Genomic Instability Laboratory, Fundación Instituto Leloir, IIBBA-CONICET Chascomús, Argentina.
Front Microbiol. 2016 May 3;7:627. doi: 10.3389/fmicb.2016.00627. eCollection 2016.
Toxoplasma gondii is an apicomplexan parasite of medical and veterinary importance which causes toxoplasmosis in humans. Great effort is currently being devoted toward the identification of novel drugs capable of targeting such illness. In this context, we believe that the thorough understanding of the life cycle of this model parasite will facilitate the identification of new druggable targets in T. gondii. It is important to exploit the available knowledge of pathways which could modulate the sensitivity of the parasite to DNA damaging agents. The homologous recombination repair (HRR) pathway may be of particular interest in this regard as its inactivation sensitizes other cellular models such as human cancer to targeted therapy. Herein we discuss the information available on T. gondii's HRR pathway from the perspective of its conservation with respect to yeast and humans. Special attention was devoted to BRCT domain-containing and end-resection associated proteins in T. gondii as in other experimental models such proteins have crucial roles in early/late steps or HRR and in the pathway choice for double strand break resolution. We conclude that T. gondii HRR pathway is a source of several lines of investigation that allow to to comprehend the extent of diversification of HRR in T. gondii. Such an effort will serve to determine if HRR could represent a potential targer for the treatment of toxoplasmosis.
刚地弓形虫是一种在医学和兽医学上具有重要意义的顶复门寄生虫，可导致人类患弓形虫病。目前人们正在大力致力于鉴定能够治疗此类疾病的新型药物。在此背景下，我们认为深入了解这种模式寄生虫的生命周期将有助于鉴定刚地弓形虫新的可成药靶点。利用有关可调节寄生虫对DNA损伤剂敏感性的信号通路的现有知识非常重要。同源重组修复（HRR）通路在这方面可能特别值得关注，因为其失活会使其他细胞模型（如人类癌症细胞）对靶向治疗敏感。在此，我们从与酵母和人类的保守性角度讨论刚地弓形虫HRR通路的现有信息。我们特别关注刚地弓形虫中含BRCT结构域和末端切除相关蛋白，因为在其他实验模型中，此类蛋白在HRR的早期/晚期步骤以及双链断裂修复的通路选择中起关键作用。我们得出结论，刚地弓形虫HRR通路是多条研究路线的来源，有助于理解刚地弓形虫中HRR的多样化程度。这样的努力将有助于确定HRR是否可能成为治疗弓形虫病的潜在靶点。
