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Formation of Linear Amplicons with Inverted Duplications in Requires the MRE11 Nuclease


Extrachromosomal DNA amplification is frequent in the human protozoan parasite Leishmania when challenged with drug or other stressful conditions. DNA amplicons, either circular or linear, are formed by recombination between direct or inverted repeats spread throughout the genome of the parasite. The recombinase RAD51 is involved in the formation of circular amplicons, but the mechanism by which linear amplicons are formed is still unknown in this parasite. Studies in other organisms have provided some evidence that a DNA break is required for linear amplifications, and that the DNA repair protein MRE11 can be involved in this process. In this work, we present our biochemical, cellular and molecular characterization of the Leishmania infantum MRE11 orthologue and provide evidence that this nuclease is involved in the formation of linear amplicons in Leishmania. Our results highlight a novel MRE11-dependent pathway used by Leishmania to amplify portions of its genome to respond to a changing environment.


Vyšlo v časopise: Formation of Linear Amplicons with Inverted Duplications in Requires the MRE11 Nuclease. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004805
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004805

Souhrn

Extrachromosomal DNA amplification is frequent in the human protozoan parasite Leishmania when challenged with drug or other stressful conditions. DNA amplicons, either circular or linear, are formed by recombination between direct or inverted repeats spread throughout the genome of the parasite. The recombinase RAD51 is involved in the formation of circular amplicons, but the mechanism by which linear amplicons are formed is still unknown in this parasite. Studies in other organisms have provided some evidence that a DNA break is required for linear amplifications, and that the DNA repair protein MRE11 can be involved in this process. In this work, we present our biochemical, cellular and molecular characterization of the Leishmania infantum MRE11 orthologue and provide evidence that this nuclease is involved in the formation of linear amplicons in Leishmania. Our results highlight a novel MRE11-dependent pathway used by Leishmania to amplify portions of its genome to respond to a changing environment.


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