Expression and characterization of human malaria parasite Plasmodium falciparum origin recognition complex subunit 1

In eukaryotes, the origin recognition complex (ORC) is essential for the initiation of DNA replication. The largest subunit of this complex (ORC1) has a regulatory role in origin activation. Here we report the cloning and functional characterization of Plasmodium falciparum ORC1 homolog. Using immun...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-11, Vol.337 (3), p.955-966
Main Authors: Mehra, Parul, Biswas, Anup K., Gupta, Ashish, Gourinath, Samudrala, Chitnis, Chetan E., Dhar, Suman K.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
ATPase
Computer Simulation
DNA replication
Erythrocytes - parasitology
Gene Expression Regulation, Developmental - physiology
Humans
Malaria, Falciparum - parasitology
Models, Chemical
Models, Molecular
Molecular Sequence Data
Origin recognition complex
Origin Recognition Complex - chemistry
Origin Recognition Complex - metabolism
Plasmodium falciparum
Plasmodium falciparum - metabolism
Plasmodium falciparum - pathogenicity
Protein Engineering - methods
Protein Subunits
Saccharomyces
Sequence Homology, Amino Acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In eukaryotes, the origin recognition complex (ORC) is essential for the initiation of DNA replication. The largest subunit of this complex (ORC1) has a regulatory role in origin activation. Here we report the cloning and functional characterization of Plasmodium falciparum ORC1 homolog. Using immunofluorescence and immunoelectron microscopy, we show here that PfORC1 is expressed in the nucleus during the late trophozoite and schizont stages where maximum amount of DNA replication takes place. Homology modelling of the carboxy terminal region of PfORC1 (781–1033) using Saccharomyces pombe Cdc6/Cdc18 homolog as a template reveals the presence of a similar AAA+ type nucleotide-binding fold. This region shows ATPase activity in vitro that is important for the origin activity. To our knowledge, this is the first evidence of an individual ORC subunit that shows ATPase activity. These observations strongly suggest that PfORC1 might be involved in DNA replication initiation during the blood stage of the parasitic life cycle.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.09.131