Comparative insight into nucleotide excision repair components of Plasmodium falciparum

Tajedin, Leila; Anwar, M. M.; Gupta, Dinesh; Tuteja, Renu

doi:10.1016/j.dnarep.2015.02.009

Cited by 10 publications

(8 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C-terminal extension of XPD harboring the interaction sites for p44 binding (Coin et al 1998) and involved in regulation of helicase activity (Compe and Egly 2012) is largely conserved between HsXPD and Plasmodium XPDs. The vWA domain, C4 zinc finger, and TFIIIA-like zinc finger/ring finger domains found in human p44 are also moderately conserved in its orthologs across all Plasmodium species (Tajedin et al (2015). It has been reported that these domains play key role in p44, the N-terminal domain is crucial for interaction with XPD, and the Cterminal ring finger domain interacts with p34, another TFII H subunit (Fribourg et al 2001;Kellenberger et al 2005) and consequently plays a role in transcription activity.…”

Section: Discussionmentioning

confidence: 98%

“…Although putative orthologues of the TFIIH subunits were previously identified in P. falciparum, but to the best of our knowledge, none of them have been functionally characterized (Bedez et al 2013;Callebaut et al 2005;Tuteja 2010;Tajedin et al 2015). Therefore, we performed studies on XPD (PlasmoDB number PF3D7_0934100) and its interacting partner, p44 (PlasmoDB number PF3D7_1314900), from P. falciparum 3D7 strain which might aid in gaining further insights into the biology of the parasite.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

2015

Self Cite

View full text Add to dashboard Cite

XPD helicase, a TFIIH subunit, is essential for several processes including transcription, NER, cell cycle regulation, and apoptosis in eukaryotes. Another component of TFIIH, namely p44, is among the well-known interacting partners of XPD and is vital in regulating the helicase activities of latter. However, none of the above mentioned proteins have been functionally characterized in Plasmodium falciparum. Consequently, in this study, we performed detailed studies on XPD and its interacting partner, p44, from P. falciparum 3D7 strain. Accordingly, we expressed and purified recombinant PfXPD and its fragments and Pfp44 proteins and characterized the enzymatic activities of PfXPD and its fragments. The in vivo stage-specific expression and subcellular localizations of PfXPD and Pfp44 proteins were studied using the specific antibodies in the intraerythrocytic developmental stages of P. falciparum 3D7 strain. Our results suggest that PfXPD displays the characteristic ssDNA-dependent ATPase and 5'-3' DNA helicase activities. We also report the existence of two high molecular weight forms of p44 in P. falciparum 3D7 strain. Both PfXPD and Pfp44 colocalize in the nucleus and interact with each other, which suggest that they are most likely components of the same complex apparently, TFIIH. Furthermore, during trophozoite and schizont stages, both proteins exhibit a distinct cytoplasmic distribution pattern which implies that PfXPD and Pfp44 might also be involved in other functions. These studies will aid in understanding the basic biology of malaria parasite.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Damage to individual bases is resolved by the excision repair pathways that include nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR). Orthologs of the majority of genes involved in the NER pathway have been identified bioinformatically, with the exception of p62 and XPC [ 73 ]. Similarly, the majority of the MMR pathway is present but there are notable differences from other eukaryotes, with RecJ exonucleases appearing to be absent while a UvrD helicase homolog, found in E. coli but absent in humans, is present [ 74 , 75 ].…”

Section: Dna Repair In Plasmodiummentioning

confidence: 99%

Checks and balances? DNA replication and the cell cycle in Plasmodium

2018

View full text Add to dashboard Cite

It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that may prove crucial for our efforts to control the disease. Phenotypic screens have partially filled the void in the antimalarial drug market, but as compound libraries eventually become exhausted, new medicines will only come from directed drug development based on a better understanding of fundamental parasite biology. This review focusses on the unusual cell cycles of Plasmodium, which may present a rich source of novel drug targets as well as a topic of fundamental biological interest. Plasmodium does not grow by conventional binary fission, but rather by several syncytial modes of replication including schizogony and sporogony. Here, we collate what is known about the various cell cycle events and their regulators throughout the Plasmodium life-cycle, highlighting the differences between Plasmodium, model organisms and other apicomplexan parasites and identifying areas where further study is required. The possibility of DNA replication and the cell cycle as a drug target is also explored. Finally the use of existing tools, emerging technologies, their limitations and future directions to elucidate the peculiarities of the Plasmodium cell cycle are discussed.

show abstract

“…The retrieved sequences were in silico studied and various domains were manually assigned and confirmed by using Pfam, Prosite, SMART, PANTHER, etc., and integrated software, InterProScan ( Quevillon et al, 2005 ). Similar to the previous reports ( Tuteja, 2010 ; Tajedin et al, 2015 ), multiple-sequence alignment was done by using ClustalW 3 and Clustal omega 4 and conserved motifs were identified manually as well as using Pfam and InterProScan software. Phylogenetic tree analysis was done by using Phylogeny.fr online available server using MUSCLE for alignment and G blocks (v0.91b) for curation of alignment to remove uncertain regions due to gaps and poor alignment.…”

Section: Methodsmentioning

confidence: 99%

Genome Wide In silico Analysis of the Mismatch Repair Components of Plasmodium falciparum and Their Comparison with Human Host

et al. 2017

Self Cite

View full text Add to dashboard Cite

Malaria a major parasitic infection globally particularly in tropical and sub-tropical regions of the world is responsible for about 198 million cases and estimated deaths due to this disease are about 0.6 million. The emergence of drug resistance in the malaria parasite is alarming and it is necessary to understand its underlying cause and molecular mechanisms. It has been established that drug resistant malaria parasites have defective mismatch repair (MMR) therefore it is essential to study this pathway and its components in detail. Recently a number of non-synonymous Single Nucleotide Polymorphisms have been reported in genes involved in MMR pathways. PfMLH is an endonuclease essential to restore the MMR in drug resistant strains of Plasmodium falciparum. Considering all these facts about the role of MMR in emergence of drug resistant parasite, in this manuscript we report a genome wide analysis of the components of the MMR pathway such as MLH, Pms1, MSH2-1, MSH2-2, MSH6, and UvrD using in silico bioinformatics based approaches. The phylogenetic analysis revealed evolutionary closeness with the MMR components of various organisms. It is noteworthy that P. falciparum contains two homologs of MSH2, which are located on different chromosomes. The structural modeling of these components showed their similarity with the human/yeast MMR components. The docking studies reveal that PfUvrD and PfMLH interact with each other. The in silico identification of interacting partners of the major MMR components identified numerous P. falciparum specific proteins. In line with our previous studies the present study will also contribute significantly to understand the MMR pathway of malaria parasite.

show abstract

Comparative insight into nucleotide excision repair components of Plasmodium falciparum

Cited by 10 publications

References 70 publications

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

Plasmodium falciparum XPD translocates in 5′ to 3′ direction, is expressed throughout the blood stages, and interacts with p44

Checks and balances? DNA replication and the cell cycle in Plasmodium

Genome Wide In silico Analysis of the Mismatch Repair Components of Plasmodium falciparum and Their Comparison with Human Host

Contact Info

Product

Resources

About