Abstract
For nearly all eukaryotic cells, stochastic DNA double-strand breaks (DSBs) are one of the most deleterious types of DNA lesions. DSB processing and repair can cause sequence deletions, loss of heterozygosity, and chromosome rearrangements resulting in cell death or carcinogenesis. However, trypanosomatids (single-celled eukaryotes parasites) do not seem to follow this premise strictly. Several studies have shown that trypanosomatids depend on DSBs to perform several events of paramount importance during their life cycle. For Trypanosoma brucei, DSBs formation is associated with host immune evasion via antigenic variation. In Trypanosoma cruzi, DSBs play a crucial role in the genetic exchange, a mechanism that is still little explored but appear to be of fundamental importance for generating variability. In Leishmania spp., DSBs are necessary to generate genomic changes by gene copy number variation (CNVs), events that are essential for these organisms to overcome inhospitable conditions. As DSB repair in trypanosomatids is primarily conducted via homologous recombination (HR), most of the events associated with DSBs are HR-dependent. This review will discuss the latest findings on how trypanosomatids balance the benefits and inexorable challenges caused by DSBs.
Highlights
DNA, the storage center of all genetic information of an organism, is continually assaulted by endogenous and exogenous sources of instability, resulting in a variety of possible injuries
double-strand breaks (DSBs) drive genomic instability leading to cell death, and if repaired incorrectly, DSBs can drastically alter the genomic structure, for example, generating chromosomal translocations and rearrangements, both of which contribute to tumorigenesis in metazoans (Kaye et al, 2004; Cannan and Pederson, 2016; Zhao et al, 2020)
Antigenic variation in T. brucei, genetic exchange in T. cruzi, and genomic alterations in Leishmania are examples of some vital processes triggered by DSBs and evidence how fundamental is this type of DNA damage for these organisms
Summary
DNA, the storage center of all genetic information of an organism, is continually assaulted by endogenous and exogenous sources of instability, resulting in a variety of possible injuries. Some studies have been evidencing DSBs as a platform to facilitate other fundamental survival mechanisms, such as increased infectivity (Silva et al, 2018; Repolês et al, 2020), chromosome/gene copy number variation (Reis-Cunha et al, 2015), and variability in multigene families (Chiurillo et al, 2016) The latter is worth highlighting for lead to evasion of host immune response, a strategy like those used by T. brucei through antigenic variation (Myler et al, 1984b; Mugnier et al, 2015). Multiple DSBs can be extremely hazardous for Leishmania spp. (Manna et al, 2010; da Silveira et al, 2013), further studies are necessary to finish the puzzle promoted by these lesions and find out when they can be a benefit or a detriment for this parasite
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