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Article

MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life

1
Queens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK
2
Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
3
The Francis Crick Institute, London NW1 1AT, UK
4
Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX1 2JD, UK
5
Department Biological & Medical Sciences, Oxford Brookes University, Oxford OX3 0BP, UK
6
Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 060-0808, Japan
*
Authors to whom correspondence should be addressed.
Current address: Leicester Cancer Research Centre, College of Life Sciences, University of Leicester, Robert Kilpatrick Building, P.O. Box 65, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
These authors contributed equally to this work.
Cells 2020, 9(12), 2590; https://doi.org/10.3390/cells9122590
Received: 3 November 2020 / Revised: 30 November 2020 / Accepted: 1 December 2020 / Published: 3 December 2020
(This article belongs to the Section Cell Signaling)
The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage 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 parasites lacking 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. Further, absence of PbMRE11 results in significant transcriptional downregulation of genes involved in key interconnected biological processes that are fundamental to all eukaryotic life including ribonucleoprotein biogenesis, spliceosome function and iron–sulfur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11′s role in Plasmodium development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission. View Full-Text
Keywords: Plasmodium; DNA repair; MRE11; malaria; ribogenesis Plasmodium; DNA repair; MRE11; malaria; ribogenesis
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MDPI and ACS Style

Guttery, D.S.; Ramaprasad, A.; Ferguson, D.J.P.; Zeeshan, M.; Pandey, R.; Brady, D.; Holder, A.A.; Pain, A.; Tewari, R. MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life. Cells 2020, 9, 2590. https://doi.org/10.3390/cells9122590

AMA Style

Guttery DS, Ramaprasad A, Ferguson DJP, Zeeshan M, Pandey R, Brady D, Holder AA, Pain A, Tewari R. MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life. Cells. 2020; 9(12):2590. https://doi.org/10.3390/cells9122590

Chicago/Turabian Style

Guttery, David S., Abhinay Ramaprasad, David J.P. Ferguson, Mohammad Zeeshan, Rajan Pandey, Declan Brady, Anthony A. Holder, Arnab Pain, and Rita Tewari. 2020. "MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life" Cells 9, no. 12: 2590. https://doi.org/10.3390/cells9122590

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