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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 |
Files in This Item:
File | Description | Size | Format | |
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Plasmodium falciparum Replication factor C 1 is involved in genotoxic stress response.pdf | main article | 768.62 kB | Adobe PDF | View/Open |
Fig_merged_RFC1.pdf | all figures | 3.76 MB | Adobe PDF | View/Open |
TableS1_Primers.pdf | table1 | 148.19 kB | Adobe PDF | View/Open |
Table S2_.pdf | table 2 | 120.1 kB | Adobe PDF | View/Open |
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