Transcription coupled repair occurrence in Trypanosoma cruzi mitochondria.

Abstract

Although several proteins involved in DNA repair systems have been identified in the T. cruzi mitochondrion, limited information is available regarding the specific DNA repair mechanisms responsible for kinetoplast DNA (kDNA) maintenance. The kDNA, contained within a single mitochondrion, exhibits a highly complex replication mechanism compared to the mitochondrial DNA of other eukaryotes. The absence of additional mitochondria makes the proper maintenance of this single mitochondrion essential for parasite viability. Trypanosomatids possess a distinct set of proteins dedicated to kDNA organization and metabolism, known as kinetoplast-associated proteins (KAPs). Despite studies identifying the localization of these proteins, their functions remain largely unclear. Here, we demonstrate that TcKAP7 is involved in the repair of kDNA lesions induced by UV radiation and cisplatin. TcKAP7 mutant cells exhibited phenotypes similar to those observed in Angomonas deanei following the deletion of this gene. This monoxenic trypanosomatid colonizes the gastrointestinal tract of insects and possesses a kinetoplast with a distinct shape and kDNA topology compared to T. cruzi, making it a suitable comparative model in this study. Additionally, we observed that DNA damage can trigger distinct signaling pathways leading to cell death. Furthermore, we elucidated the involvement of CSB in this response, suggesting a potential interaction between TcKAP7 and CSB proteins in transcription-coupled DNA repair. The results presented here describe, for the first time, the mechanism of mitochondrial DNA repair in trypanosomatids following exposure to UV radiation and cisplatin.