scholarly journals Plasmodium falciparum replication factor C subunit 1 is involved in genotoxic stress response

2020 ◽  
Author(s):  
Omar Sheriff ◽  
Aniweh Yaw ◽  
Soak Kuan Lai ◽  
hooi linn loo ◽  
Siu Kwan Sze ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Stress Response ◽  
Genotoxic Stress ◽  
Replication Factor C ◽  
Replication Factor ◽  
C Subunit ◽  
Factor C

scholarly journals A genetic analysis of the 63E-64A genomic region of Drosophila melanogaster: identification of mutations in a replication factor C subunit.

Genetics ◽  
1995 ◽  
Vol 139 (4) ◽  
pp. 1701-1709 ◽  
Author(s):  
S D Harrison ◽  
N Solomon ◽  
G M Rubin
Keyword(s):  
Complementation Group ◽  
Genomic Region ◽  
Replication Factor C ◽  
Group 13 ◽  
Multiple Alleles ◽  
Replication Factor ◽  
Lethal Mutations ◽  
C Subunit ◽  
Complementation Groups ◽  
Factor C

Abstract We have performed an F2 genetic screen to identify lethal mutations within the 63E-64A genomic region. We have isolated 122 mutations in 20 different complementation groups. Of these groups, 16 are represented by multiple alleles. We have also established that the Rop and Ras2 genes are located within the 63E-64A genomic domain at 64A10,11. We have sequenced 10.2 kb of DNA surrounding this gene pair and find that in addition to Rop and Ras2 there is another gene located within this DNA sequence. The gene product, which we have named Rfc40, shows 68% identity to the 40-kDa subunit of replication factor C. We find that the members of one complementation group (13 alleles) derived from our screen correspond to mutations in the Rop gene, whereas the members of another (five alleles) correspond to mutations in the Rfc40 gene. In addition we have isolated 11 new mutant alleles of the disembodied gene.

scholarly journals MicroRNA‑744‑5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

2021 ◽  
Vol 22 (2) ◽  
Author(s):  
Fei Fan ◽  
Dongxiao Yao ◽  
Pengfei Yan ◽  
Xiaobing Jiang ◽  
Jie Hu
Keyword(s):  
Replication Factor C ◽  
Replication Factor ◽  
C Subunit ◽  
Factor C

scholarly journals Inactivating pentapeptide insertions in the fission yeast replication factor C subunit Rfc2 cluster near the ATP-binding site and arginine finger motif

FEBS Journal ◽  
2009 ◽  
Vol 276 (17) ◽  
pp. 4803-4813 ◽  
Author(s):  
Fiona C. Gray ◽  
Kathryn A. Whitehead ◽  
Stuart A. MacNeill
Keyword(s):  
Binding Site ◽  
Fission Yeast ◽  
Atp Binding ◽  
Replication Factor C ◽  
Atp Binding Site ◽  
Replication Factor ◽  
C Subunit ◽  
Factor C ◽  
Arginine Finger

scholarly journals Plasmodium falciparum Replication factor C subunit 1 is involved in genotoxic stress response

2020 ◽  
Author(s):  
O Sheriff ◽  
Y Aniweh ◽  
Soak-Kuan Lai ◽  
HL Loo ◽  
S. K Sze ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Dna Repair ◽  
Plasmodium Falciparum ◽  
Stress Response ◽  
Programmed Cell Death ◽  
Genotoxic Stress ◽  
Antimalarial Drugs ◽  
Protein Levels ◽  
Factor C

AbstractAbout 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 protein is an important component of the DNA replication machinery and DNA damage response mechanism. Here we show the translocation of PfRFC1 from an intranuclear localization 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 and DNA repair pathways leading to cell death. Additionally, mislocalization 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 plasmodium falciparum.ImportanceFrontline drugs have been found to induce DNA damage in the human malaria parasite Plasmodium falciparum. The genotoxic stress response in Plasmodium and the interplay between DNA damage repair, replication and activation of programmed cell death pathways remains largely undescribed. This study shows a distinct pattern of localization of PfRFC1 during replication and DNA repair. PfRFC1 responds to genotoxic stress with an increase in protein expression. Interfering with the RFC complex formation or mislocalization of PfRFC1 is associated with disrupted genotoxic stress response. Additionally, a reduction of PfRFC1 protein levels is observed upon treatment with antimalarial drugs or under apoptosis like conditions, highlighting the role of DEVD/G like motif in mediating programmed cell death in these parasites. This study sheds light on the role of PfRFC1 in differentially responding to replication, genotoxic stress and programmed cell death in Plasmodium parasites.

scholarly journals Forkhead box O1 targeting replication factor C subunit 2 expression promotes glioma temozolomide resistance and survival

2021 ◽  
Vol 9 (8) ◽  
pp. 692-692
Author(s):  
Xingsheng Qiu ◽  
Guifeng Tan ◽  
Hao Wen ◽  
Lian Lian ◽  
Songhua Xiao
Keyword(s):  
Replication Factor C ◽  
Replication Factor ◽  
Forkhead Box ◽  
C Subunit ◽  
Factor C

scholarly journals The absence of F-box motif Encoding Gene SAF1 and Chromatin Associated factor CTF8 together contributes to MMS Resistant and HU Sensitive phenotype in S. cerevisiae

2019 ◽  
Author(s):  
Meenu Sharma ◽  
V. Verma ◽  
Narendra K Bairwa
Keyword(s):  
Genetic Interaction ◽  
E3 Ligase ◽  
Genotoxic Stress ◽  
Chromosome Loss ◽  
Quiescent State ◽  
Replication Factor C ◽  
Differential Growth ◽  
Replication Factor ◽  
Growth Phenotype ◽  
Factor C

AbstractThe Replication factor-C compex which related to cohesion, constitutes, three subunits called Ctf18, Ctf8 and Dcc1. These three subunit complex assist the loading of PCNA onto the chromosome. None of the replication factor C components are essential for cell viability. The null mutant of the CTF8 in S.cerevisiae shows the chromosome instability and high frequency of chromosome loss. The SAF1 gene product of S. cerevisiae involved in the degradation of adenine deaminase factor Aah1p by SCF-E3 ligase, which itself is the part of E3 ligase. The ubiquitin marked degradation of Aah1p occurs during nutrient stress which lead to cell enter into the quiescent state. The N-terminus of Saf1p interacts with the Skp1 of SCF-E3 ligase and at C-terminus recruits with Aah1p. Here we have investigated about the binary genetic interaction between the SAF1 and CTF8 genes. The strains containing single and double gene deletions of SAF1 and CTF8 were constructed in the BY4741 genetic background. Further the mutant strains were evaluated for growth fitness, genome stability and response to genotoxic stress caused by hydroxyurea (HU) and methyl methane sulfonate (MMS). The saf1Δctf8Δ strain showed the increased growth phenotype in comparison to saf1Δ, ctf8Δ, and WT strain on YPD medium. However saf1Δctf8Δ strain when grown in the presence MMS showed resistance and HU sensitive phenotype when compared with saf1Δ, ctf8Δ. The frequency of Ty1 retro-transposition was also elevated in saf1Δctf8Δ in comparison to either saf1Δ or ctf8Δ. The number of cells showing the two or multi-nuclei phenotype was also increased in saf1Δctf8Δ cells when compared with the either saf1Δ or ctf8Δ. Based on these observations, we report that the absence of both the gene SAF1 and CTF8 together leads to MMS resistance, HU sensitivity, and genome instability. This report warrants the investigation of mechanisms of differential growth phenotype due to loss of SAF1 and CTF8 together in presence of genotoxic stress in future.

scholarly journals Replication Factor C Subunit 4

2020 ◽  
Author(s):  
Keyword(s):  
Replication Factor C ◽  
Replication Factor ◽  
C Subunit ◽  
Factor C

scholarly journals The Large Subunit of Replication Factor C (Rfclp/Cdc44p) Is Required for DNA Replication and DNA Repair in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Michael A McAlear ◽  
K Michelle Tuffo ◽  
Connie Holm
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Dna Replication ◽  
Uv Radiation ◽  
Large Subunit ◽  
Restrictive Temperature ◽  
Replication Factor C ◽  
Replication Factor ◽  
Factor C

We used genetic and biochemical techniques to characterize the phenotypes associated with mutations affecting the large subunit of replication factor C (Cdc44p or Rfc1p) in Saccharomyces cerevisiae. We demonstrate that Cdc44p is required for both DNA replication and DNA repair in vivo. Cold-sensitive cdc44 mutants experience a delay in traversing S phase at the restrictive temperature following alpha factor arrest; although mutant cells eventually accumulate with a G2/M DNA content, they undergo a cell cycle arrest and initiate neither mitosis nor a new round of DNA synthesis. cdc44 mutants also exhibit an elevated level of spontaneous mutation, and they are sensitive both to the DNA damaging agent methylmethane sulfonate and to exposure to UV radiation. After exposure to UV radiation, cdc44 mutants at the restrictive temperature contain higher levels of single-stranded DNA breaks than do wild-type cells. This observation is consistent with the hypothesis that Cdc44p is involved in repairing gaps in the DNA after the excision of damaged bases. Thus, Cdc44p plays an important role in both DNA replication and DNA repair in vivo.

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