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
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: embargo_20220228
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
Plasmodium falciparum Replication factor C 1 is involved in genotoxic stress response.pdf
  Until 2022-02-28
main article768.62 kBAdobe PDFUnder embargo until Feb 28, 2022
Fig_merged_RFC1.pdf
  Until 2022-02-28
all figures3.76 MBAdobe PDFUnder embargo until Feb 28, 2022
TableS1_Primers.pdf
  Until 2022-02-28
table1148.19 kBAdobe PDFUnder embargo until Feb 28, 2022
Table S2_.pdf
  Until 2022-02-28
table 2120.1 kBAdobe PDFUnder embargo until Feb 28, 2022

Page view(s)

117
Updated on Jan 22, 2022

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.