Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana.

Autor: Poláková E; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic., Albanaz ATS; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic., Zakharova A; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic., Novozhilova TS; Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia., Gerasimov ES; Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia.; Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia., Yurchenko V; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic.; Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russia.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2021 Dec 29; Vol. 15 (12), pp. e0010041. Date of Electronic Publication: 2021 Dec 29 (Print Publication: 2021).
DOI: 10.1371/journal.pntd.0010041
Abstrakt: Background: Telomeres are indispensable for genome stability maintenance. They are maintained by the telomere-associated protein complex, which include Ku proteins and a telomerase among others. Here, we investigated a role of Ku80 in Leishmania mexicana. Leishmania is a genus of parasitic protists of the family Trypanosomatidae causing a vector-born disease called leishmaniasis.
Methodology/principal Findings: We used the previously established CRISPR/Cas9 system to mediate ablation of Ku80- and Ku70-encoding genes in L. mexicana. Complete knock-outs of both genes were confirmed by Southern blotting, whole-genome Illumina sequencing, and RT-qPCR. Resulting telomeric phenotypes were subsequently investigated using Southern blotting detection of terminal restriction fragments. The genome integrity in the Ku80- deficient cells was further investigated by whole-genome sequencing. Our work revealed that telomeres in the ΔKu80 L. mexicana are elongated compared to those of the wild type. This is a surprising finding considering that in another model trypanosomatid, Trypanosoma brucei, they are shortened upon ablation of the same gene. A telomere elongation phenotype has been documented in other species and associated with a presence of telomerase-independent alternative telomere lengthening pathway. Our results also showed that Ku80 appears to be not involved in genome stability maintenance in L. mexicana.
Conclusion/significance: Ablation of the Ku proteins in L. mexicana triggers telomere elongation, but does not have an adverse impact on genome integrity.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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