AUK3 is required for faithful nuclear segregation in the bloodstream form of Trypanosoma brucei
Year: 2024
Type: article
Abstract: Eukaryotic chromosomes segregate faithfully prior to nuclear division to ensure genome stability. If segregation becomes defective, the chromosome copy number of the cell may alter leading to aneuploidy and/or polyploidy, both common hallmarks of cancers. In eukaryotes, aurora kinases regulate chromosome segregation during mitosis and meiosis, but their functions in the divergent, single-celled eukaryotic pathogen Trypanosoma brucei are less understood. Here, we focused on one of three aurora kinases in these parasites, TbAUK3, a homologue of the human aurora kinase AURKC, whose functions are primarily restricted to meiosis. We show that RNAi targeted depletion of TbAUK3 correlates with nuclear segregation defects, reduced proliferation, and decreased DNA synthesis, suggestive of a role for TbAUK3 during mitotic, not meiotic, chromosome segregation. Moreover, we uncover a putative role for TbAUK3 during the parasite's response to DNA damage since we show that depletion of TbAUK3 enhances DNA instability and sensitivity to genotoxic agents.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,260
Awards: How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?, G1309769649, G1571693581, Does genome replication in Leishmania rely on origin-independent initiation?, G1955287037, Of epigenetics, genomic variability and gene expression regulation in Leishmania, G4119018226, A distinct mode of DNA replication initiation in trypanosomes?, Wellcome Trust Centre for Molecular Parasitology., G4680533948, UK:Brazil Joint Centre Partnership in leishmaniasis, G5300353797, Understanding the DNA replication programmes of the African trypanosome and Leishmania
OpenAlex ID: W4405941795