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Πέμπτη 19 Ιουλίου 2018

Role of tyrosine residue (Y213) in nuclear retention of PCNA1 in human malaria parasite Plasmodium falciparum

Abstract
Proliferating Cell Nuclear Antigen (PCNA) undergoes several Post Translational Modifications including phosphorylation leading to its regulation in mammalian and yeast systems. Plasmodium falciparum possesses two PCNAs (PCNA1 & PCNA2) with an edge of PfPCNA1 over PfPCNA2 for DNA replication. Recent phosphoproteome data report phosphorylation of S191 residue without its functional implication. In mammalian cells, phosphorylation of HsPCNA at Y211 stabilizes chromatin bound PCNA. We find tyrosine (but not S191) to be conserved in PfPCNAs and it is important for its nuclear localization and foci formation of PfPCNA1. Further, a Y213F mutation in PfPCNA1 leads to its functional loss both in yeast and parasite. We highlight the importance of evolutionarily conserved tyrosine in PCNA from parasite to mammal linked with DNA replication and cell proliferation.

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