Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/148492
Title: Plasmodium falciparum replication factor C subunit 1 is involved in genotoxic stress response
Authors: Sheriff, Omar
Yaw, Aniweh
Lai, Soak Kuan
Loo, Hooi Linn
Sze, Siu Kwan
Preiser, Peter Rainer
Keywords: Science::Biological sciences
Issue Date: 2021
Source: Sheriff, O., Yaw, A., Lai, S. K., Loo, H. L., Sze, S. K. & Preiser, P. R. (2021). Plasmodium falciparum replication factor C subunit 1 is involved in genotoxic stress response. Cellular Microbiology, 23(2), e13277-. https://dx.doi.org/10.1111/cmi.13277
Project: CBRG12nov014, OFIRG17may073
NGF‐2017‐03‐032
Journal: Cellular Microbiology
Abstract: About half the world's population is at risk of malaria, with Plasmodium falciparum malaria being responsible for the most malaria related deaths globally. Antimalarial drugs such as chloroquine and artemisinin are directed towards the proliferating intra-erythrocytic stages of the parasite, which is responsible for all the clinical symptoms of the disease. These antimalarial drugs have been reported to function via multiple pathways, one of which induces DNA damage via the generation of free radicals and reactive oxygen species. An urgent need to understand the mechanistic details of drug response and resistance is highlighted by the decreasing clinical efficacy of the front line drug, Artemisinin. The replication factor C subunit 1 is an important component of the DNA replication machinery and DNA damage response mechanism. Here we show the translocation of PfRFC1 from an intranuclear localisation to the nuclear periphery, indicating an orchestrated progression of distinct patterns of replication in the developing parasites. PfRFC1 responds to genotoxic stress via elevated protein levels in soluble and chromatin bound fractions. Reduction of PfRFC1 protein levels upon treatment with antimalarials suggests an interplay of replication, apoptosis and DNA repair pathways leading to cell death. Additionally, mislocalisation of the endogenously tagged protein confirmed its essential role in parasites' replication and DNA repair. This study provides key insights into DNA replication, DNA damage response and cell death in P. falciparum.
URI: https://hdl.handle.net/10356/148492
ISSN: 0021-843X
DOI: 10.1111/cmi.13277
Schools: School of Biological Sciences 
Rights: This is the peer reviewed version of the following article: Sheriff, O., Yaw, A., Lai, S. K., Loo, H. L., Sze, S. K. & Preiser, P. R. (2021). Plasmodium falciparum replication factor C subunit 1 is involved in genotoxic stress response. Cellular Microbiology, 23(2), e13277-. https://dx.doi.org/10.1111/cmi.13277, which has been published in final form at https://doi.org/10.1111/cmi.13277. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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