Pre-replication complex organization in the atypical DNA replication cycle of Plasmodium falciparum: Characterization of the mini-chromosome maintenance (MCM) complex formation

Patterson, Shelley; Robert, Claudia E.; Whittle, Christina M.; Chakrabarti, Ratna; Doerig, Christian; Chakrabarti, Debopam

doi:10.1016/j.molbiopara.2005.09.006

Cited by 18 publications

(40 citation statements)

References 39 publications

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“…In fact, differences in CDK regulation are responsible for maintaining either a "normal" mitotic cell cycle versus an endocycle by controlling the assembly and firing of the pre-RC [53]. Many components of the pre-RC and RC are encoded in the plasmodial genome and several have been characterized including MCMs, ORCs, DNA polymerases and PCNA [31,[54][55][56][57][58]. Although the in vivo phosphorylation status of these DNA replication components remains to be investigated, it is tempting to speculate that Pfmrk-mediated phosphorylation of PfRFC-5 and PfMCM6 may regulate the initiation of DNA replication.…”

Section: Discussionmentioning

confidence: 99%

“…The microarray data of Pfmrk, PfMAT1 and Pfcyc-1 suggest high levels of expression from 4 to 28 h peaking at 8 and 24 h-several hours before the start of DNA replication [59]. PfMCM6 protein has been predominantly detected in late trophozoites and schizonts, and gene expression of both PfMCM-6 and PfRFC-5 peaks in late trophozoites through early schizonts-stages where most DNA replication is thought to occur [31,60].…”

Section: Discussionmentioning

confidence: 99%

“…All two-hybrid interactions were verified in at least three independent clones. From our list of four two-hybrid hits, we selected the already characterized mini chromosome maintenance protein-6 (PfMCM6) (PF13 0291) [31] and the replication factor complex subunit five (RFC-5) (PF11 0117) for further analyses. Full length PfRFC-5 and PfMCM6 were subsequently cloned into the pTRG vector via RT-PCR and their interactions with Pfmrk were confirmed through a positive validation two-hybrid screen (Stratagene).…”

Section: Bacteriomatch Two-hybrid Screenmentioning

confidence: 99%

“…The MCM com- plex has been shown to play a key role in the transition of the pre-RC to the RC and is known to function as a replicative helicase [19]. PfMCM6 was shown to be associated with chromatin at every stage of the parasite's intraerythrocytic life stage [31].…”

Section: Pfrfc-5 and Pfmcm6 Interact With Pfmrk In The Bacterial Two-mentioning

confidence: 99%

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The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus

Jirage

Chen

Caridha

et al. 2010

Molecular and Biochemical Parasitology

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a b s t r a c tCyclin-dependent kinases (CDKs) have an established role in metazoans and yeast in DNA replication, transcription and cell cycle regulation. Several CDKs and their effectors have been identified in the malaria parasite Plasmodium falciparum and their biological functions are beginning to be investigated. Here we report results from the functional characterization of Pfmrk and its effector PfMAT1. We validated the interactions between Pfmrk and PfMAT1 and pinpointed their intracellular location. Co-immunoprecipitation studies demonstrated physical interaction between the two proteins and identified the C-terminal domain of PfMAT1 as the Pfmrk activator domain. Immunofluorescence analyses using GFP and RFP-tagged versions of Pfmrk and PfMAT1, respectively, demonstrated the co-localization of these two proteins to the parasite nucleus. Bacterial two-hybrid screen of a P. falciparum cDNA library using Pfmrk as the bait identified two plasmodial DNA replication proteins, PfRFC-5 and PfMCM6, as interactors with Pfmrk. We demonstrate that that these two proteins are substrates of Pfmrk-mediated phosphorylation and that PfMAT1 confers substrate specificity to the Pfmrk kinase complex. Collectively, these data suggest a role for Pfmrk in the nucleus of the parasite presumably in regulation of the DNA replication machinery.Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Bacteriomatch Two-hybrid Screenmentioning

confidence: 99%

Section: Pfrfc-5 and Pfmcm6 Interact With Pfmrk In The Bacterial Two-mentioning

confidence: 99%

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The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus

Jirage

Chen

Caridha

et al. 2010

Molecular and Biochemical Parasitology

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show abstract

“…ORC1 and MCM4 have role in pre-replication formation and both expressed only in gametocytes [15,16]. However all six subunits of the MCM complex has been reported in P. falciparum [17]. There are 8 MCM (2-9) present in P. falciparum [18].…”

Section: Introductionmentioning

confidence: 99%

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2018

RJLBPCS

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Genome-wide binding sites of Plasmodium falciparum mini chromosome maintenance protein MCM6 show new insights into parasite DNA replication

Shekhar

Verma

Gupta

et al. 2023

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Pre-replication complex organization in the atypical DNA replication cycle of Plasmodium falciparum: Characterization of the mini-chromosome maintenance (MCM) complex formation

Cited by 18 publications

References 39 publications

The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus

The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus

Untitled

Genome-wide binding sites of Plasmodium falciparum mini chromosome maintenance protein MCM6 show new insights into parasite DNA replication

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