Certain amplified genomic-DNA fragments (AGFs) may be involved in cell cycle progression and chloroquine is found to induce the production of cell-cycle-associated AGFs (CAGFs) in Plasmodium falciparum

TL;DR

This study proposes that amplified genomic-DNA fragments (AGFs), termed CAGFs, are involved in cell cycle regulation and are induced by chloroquine in Plasmodium falciparum, potentially explaining its antimalarial effects.

Contribution

It introduces the novel concept that specific amplified genomic-DNA fragments (CAGFs) are involved in cell cycle progression and are modulated by chloroquine in P. falciparum.

Findings

Chloroquine induces production of CAGFs in P. falciparum.

CAGFs may regulate gene expression and genome architecture during the cell cycle.

Proposes a new mechanism for chloroquine's action involving CAGFs.

Abstract

It is well known that cyclins are a family of proteins that control cell-cycle progression by activating cyclin-dependent kinase. Based on our experimental results, we propose here a novel hypothesis that certain amplified genomic-DNA fragments (AGFs) may also be required for the cell cycle progression of eukaryotic cells and thus can be named as cell-cycle-associated AGFs (CAGFs). Like fluctuation in cyclin levels during cell cycle progression, these CAGFs are amplified and degraded at different points of the cell cycle. The functions of CAGFs are unknown, but we speculate that CAGFs might be involved in regulation of gene expression, genome protection, and formation of certain macromolecular complexes required for the dynamic genome architecture during cell cycle progression. Our experimental results also show that chloroquine induces the production of CAGFs in Plasmodium falciparum, suggesting that targeting cell cycle progression can be the primary mechanism of chloroquine's antimalarial, anticancer, and immunomodulatory actions.