Premium
Regulation of P lasmodium falciparum O rigin R ecognition C omplex subunit 1 ( PfORC 1) function through phosphorylation mediated by CDK ‐like kinase PK 5
Author(s) -
Deshmukh Abhijit S.,
Agarwal Meetu,
Mehra Parul,
Gupta Ashish,
Gupta Nidhi,
Doerig Christian D.,
Dhar Suman Kumar
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13099
Subject(s) - biology , origin recognition complex , microbiology and biotechnology , cyclin dependent kinase , protein subunit , dna replication , phosphorylation , gene , cell cycle , eukaryotic dna replication , genetics
Summary P lasmodium falciparum O rigin R ecognition C omplex subunit 1 ( PfORC 1) has been implicated in DNA replication and var gene regulation. While the C ‐terminus is involved in DNA replication, the specific role of N ‐terminus has been suggested in var gene regulation in a S ir2‐dependent manner. PfORC 1 is localized at the nuclear periphery, where the clustering of chromosomal ends at the early stage of parasite development may be crucial for the regulation of subtelomeric var gene expression. Upon disassembly of telomeric clusters at later stages of parasite development, ORC 1 is distributed in the nucleus and parasite cytoplasm where it may be required for its other cellular functions including DNA replication. The level of ORC 1 decreases dramatically at the late schizont stage. The mechanisms that mediate regulation of PfORC 1 function are largely unknown. Here we show, by the use of recombinant proteins and of transgenic parasites expressing wild type or mutant forms of ORC 1, that phosphorylation of the PfORC 1‐ N terminal domain by the cyclin‐dependent kinase ( CDK ) PfPK 5 abolishes DNA ‐binding activity and leads to changes in subcellular localization and proteasome‐mediated degradation of the protein in schizonts. These results reveal that PfORC 1 phosphorylation by a CDK is central to the regulation of important biological functions like DNA replication and var gene silencing.