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
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 may 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.
Cite this paper
Li, G. (2016). 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. Open Access Library Journal, 3, e2447. doi: http://dx.doi.org/10.4236/oalib.1102447.
Li, G.D. (2006) Nucleus May
Be the Key Site of Chloroquine Antimalarial Action and Resistance Development. Medical Hypotheses, 67, 323-326. http://dx.doi.org/10.1016/j.mehy.2006.02.008
Li, G.D. (2007) Plasmodium falciparum Chloroquine
Resistance Marker Protein (Pfcrmp) May Be a Chloroquine Target Protein in Nucleus. Medical Hypotheses, 68, 332-334. http://dx.doi.org/10.1016/j.mehy.2006.07.016
Evans, T., Rosenthal, E.T., Youngblom, J.,
Distel, D. and Hunt, T. (1983) Cyclin: A
Protein Specified by Maternal mRNA in Sea Urchin Eggs That Is Destroyed at Each
Cleavage Division. Cell, 33, 389-396. http://dx.doi.org/10.1016/0092-8674(83)90420-8
Ravitz, M.J. and Wenner, C.E. (1997) Cyclin-Dependent Kinase
Regulation during G1 Phase and Cell Cycle Regulation by TGF-Beta. Advances in Cancer Research, 71, 165-207. http://dx.doi.org/10.1016/S0065-230X(08)60099-8
Lim, S. and Kaldis, P. (2013) Cdks, Cyclins and CKIs: Roles beyond
Cell Cycle Regulation. Development, 140, 3079- 3093. http://dx.doi.org/10.1242/dev.091744
Sasaki, K., Tsuno, N.H., Sunami, E., Tsurita, G., Kawai, K., Okaji, Y., et al. (2010) Chloroquine Potentiates the Anti-Cancer
Effect of 5-Fluorouracil on Colon Cancer Cells. BMC Cancer, 10, 370. http://dx.doi.org/10.1186/1471-2407-10-370
O’Brien, R.L., Olenick, J.G. and Hahn, F.E. (1966) Reactions of Quinine, Chloroquine, and Quinacrine with DNA and Their
Effects on the DNA and RNA Polymerase Reactions. Proceedings of the National Academy of Sciences of the United States of
America, 55, 1511-1517. http://dx.doi.org/10.1073/pnas.55.6.1511
Maeda, S., Lin, K.H., Inagaki, H. and Saito, T. (1996) Induction of Apoptosis in Primary
Culture of Rat Hepatocytes by Protease Inhibitors. Biochemistry and Molecular Biology International Journal, 39, 447-453.
Picot, S.,
Burnod, J., Bracchi, V., Chumpitazi, B.F. and
Ambroise-Thomas, P. (1997) Apoptosis Related to Chloroquine Sensitivity of the
Human Malaria Parasite Plasmodium
falciparum. Transactions of the Royal
Society of Tropical Medicine and Hygiene, 91, 590-591. http://dx.doi.org/10.1016/S0035-9203(97)90039-0
Arnot, D.E. and Gull, K. (1998) The Plasmodium Cell-Cycle:
Facts and Questions. Annals of
Tropical Medicine and Parasitology, 92, 361-365. http://dx.doi.org/10.1080/00034989859357
Inselburg, J. and Banyal,
H.S. (1984) Synthesis of DNA during the Asexual Cycle of Plasmodium falciparum in Culture. Molecular and Biochemical Parasitology, 10, 79-87. http://dx.doi.org/10.1016/0166-6851(84)90020-3
Lanctot, C., Cheutin, T., Cremer, M., Cavalli, G. and Cremer,
T. (2007) Dynamic Genome Architecture in the Nuclear Space: Regulation of Gene
Expression in Three Dimensions. Nature
Reviews Genetics, 8, 104-115. http://dx.doi.org/10.1038/nrg2041
Westenberger, S.J., Cui, L., Dharia, N., Winzeler,
E. and Cui, L. (2009) Genome-Wide Nucleosome Mapping of Plasmodium falciparum Reveals
Histone-Rich Coding and Histone-Poor Intergenic Regions and Chromatin Remodeling
of Core and Subtelomeric Genes. BMC
Genomics, 10,
610. http://dx.doi.org/10.1186/1471-2164-10-610
Weiner, A., Dahan-Pasternak, N., Shimoni, E.,
Shinder, V., von Huth, P., Elbaum, M. and Dzikowski, R.
(2011) 3D Nuclear Architecture Reveals Coupled Cell Cycle Dynamics of Chromatin
and Nuclear Pores in the Malaria Parasite Plasmodium
falciparum. Cellular Microbiology,
13, 967-977. http://dx.doi.org/10.1111/j.1462-5822.2011.01592.x
Ay, F., Bunnik, E.M., Varoquaux, N., Bol, S.M., Prudhomme, J., Vert, J.P., Noble, W.S. and Le Roch, K.G. (2014)
Three-Dimensional Modeling of the P.
falciparum Genome during the Erythrocytic Cycle Reveals a Strong Connection
between Genome Architecture and Gene Expression. Genome Research, 24, 974-988. http://dx.doi.org/10.1101/gr.169417.113
Nilkaeo, A., Bhuvanath,
S., Praputbut, S. and Wisessombat, S.
(2006) Induction of Cell Cycle Arrest and Apoptosis in JAR Trophoblast by
Antimalarial Drugs. Biomedical Research,
27, 131-137. http://dx.doi.org/10.2220/biomedres.27.131
Jiang, P.D., Zhao, Y.L., Shi, W., Deng, X.Q.,
Xie, G., Mao, Y.Q., et al. (2008)
Cell Growth Inhibition, G2/M Cell Cycle Arrest, and Apoptosis Induced
by Chloroquine in Human Breast Cancer Cell Line Bcap-37. Cellular Physiology and Biochemistry, 22, 431-440. http://dx.doi.org/10.1159/000185488