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. 2023 Jan 26;13:1102462. doi: 10.3389/fcimb.2023.1102462

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Copyright © 2023 Black, Reis-Cunha, Cruz and Tosi

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Putative models of extrachromosomal amplification in Leishmania driven by DNA Repeats. In Leishmania, extrachromosomal DNA amplification can be catalysed by either Direct Repeats (DRs) or Inverted Repeats (IR). Though the precise trigger(s) are unknown, putative sources of DNA instability are listed in the corresponding box above that may contribute to DNA amplification in Leishmania. Recombination reactions associated with DRs can result in tandem duplications and circular amplicons. The recombinase RAD51 facilitates a homology driven recombination between DRs that may result in (A) a tandem duplication, or (B) extrachromosomal circular amplicons. The mechanism driving tandem duplication events is unclear and may be the result of Break Induced Replication (BIR) or form an uneven exchange of genetic information between sister chromatids. Black arrows = DRs, (?) = the involvement of this factor or pathway requires experimental confirmation, Blue Cross indicates homologous recombination. (C) Linear amplification is driven through an annealing reaction between IRs. Here, the exonuclease activity of Mre11 may process a DNA lesion, for example a single strand break, or a hairpin structure formed due to DNA replication, after which the IRs anneal, and the DNA is replicated. Double arrows = telomeric sequences. Black arrows = IRs. Diagram adapted from (Laffitte et al., 2016b).