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MRE11 is crucial for malaria transmission and its absence affects expression of interconnected networks of key genes essential for life
Ferguson, David J P
Holder, Anthony A.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Pathogen Genomics Laboratory
Permanent link to this recordhttp://hdl.handle.net/10754/664833.1
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AbstractThe Meiotic Recombination 11 protein (MRE11) plays a key role during the DNA damage repair response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite Plasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis of Plasmodium MRE11 during its life-cycle in both mammalian and mosquito vector hosts. Genetic disruption of Plasmodium berghei mre11 (PbMRE11) results in significant retardation of oocyst development in the mosquito midgut associated with cytoplasmic and nuclear degeneration, along with concomitant ablation of sporogony and subsequent parasite transmission. We also highlight that absence of PbMRE11 results in significant transcriptional downregulation of genes comprising key interconnected biological networks that are fundamental to all eukaryotic life including ribonucleoprotein and iron-sulphur cluster biogenesis, spliceosome function, as well as parasite cell adhesion. Overall, our study provides the first functional analysis of MRE11s role in Plasmodium development and offers a potential target for therapeutic intervention during malaria parasite transmission.
CitationGuttery, D., Ramaprasad, A., Ferguson, D., Zeeshan, M., Pandey, R., Brady, D., … Tewari, R. (2020). MRE11 is crucial for malaria transmission and its absence affects expression of interconnected networks of key genes essential for life. doi:10.1101/2020.08.24.258657
PublisherCold Spring Harbor Laboratory