Polo-like kinase 1 (Plk1): An Unexpected Player in DNA Replication

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA. .
Cell Division (Impact Factor: 3.53). 02/2012; 7(1):3. DOI: 10.1186/1747-1028-7-3
Source: PubMed

ABSTRACT Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. It is well established that Polo-like kinase 1 (Plk1) plays critical roles in mitosis but little is known about its functions at other stages of the cell cycle. Here we summarize the functions of Plk1 during DNA replication, focusing on the molecular events related to Origin Recognition Complex (ORC), the complex that is essential for the initiation of DNA replication. Within the context of Plk1 phosphorylation of Orc2, we also emphasize regulation of Orc2 in different organisms. This review is intended to provide some insight into how Plk1 coordinates DNA replication in S phase with chromosome segregation in mitosis, and orchestrates the cell cycle as a whole.

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Available from: X. Shawn Liu, Jul 29, 2015
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    • "This pattern is consistent with previous studies showing that p53 protein transcriptionally represses CDC20 at the mRNA level in different types of DNA damaged cells (Banerjee et al., 2009; Kidokoro et al., 2008). We also observed reduced expression of polo-like kinase 1 (PLK1), a critical regulator of cell cycle progression and checkpoint modulation in response to DNA damage (Bahassi, 2011; Song et al., 2012). The reduced levels of PLK1 in Vero cells treated with Mix 100 could merely reflect the observed cell cycle arrest at G1/S transition , because peak expression of PLK1 mRNA and protein occurs in M phase (Uchiumi et al., 1997). "
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    ABSTRACT: Butylated hydroxyanisole and propylparaben are phenolic preservatives commonly used in food, pharmaceutical and personal care products. Both chemicals have been subjected to extensive toxicological studies, due to the growing concern regarding their possible impacts on environmental and human health. However, the cytotoxicity and underlying mechanisms of co-exposure to these compounds have not been explored. In this study, a set of relevant cytotoxicity endpoints including cell viability and proliferation, oxidative stress, DNA damage and gene expression changes were analyzed to assess whether the antioxidant butylated hydroxyanisole could prevent the pro-oxidant effects caused by propylparaben in Vero cells. We demonstrated that binary mixtures of both chemicals induce greater cytotoxic effects than those reported after single exposureto each compound. Simultaneous treatment with butylated hydroxyanisole and propylparaben caused G0/G1 cell cycle arrest as a result of enhanced generation of oxidative stress and DNA double strand breaks. DNA microarray analysis revealed that a cross-talk between transforming growth factor beta (TGFβ) and ataxia-telangiectasia mutated kinase (ATM) pathways regulates the response of Vero cells to the tested compounds in binary mixture. Our findings indicate that butylated hydroxyanisole potentiates the pro-oxidant effects of propylparaben in cultured mammalian cells and provide useful information for their safety assessment.
    Food and Chemical Toxicology 07/2014; 72. DOI:10.1016/j.fct.2014.07.031 · 2.90 Impact Factor
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    • "All these Plk1 activities are associated with its subcellular localization. In interphase (G 1 , S, G 2 ), Plk1 is involved in DNA replication and centrosome maturation [13] [14], in prophase to mitotic entry [15] [16], in prometaphase and metaphase, Plk1 might be involved in spindle assembly/formation and at telephase, it acts as a key regulator of cytokinesis [17]. Hence, downregulation of Plk1 activity promotes cell cycle arrest and apoptosis [18] [19]. "
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    ABSTRACT: Molecular modeling studies were carried out for a series of benzimidazole and imidazo[1,2-a]pyridines as Plk1 inhibitors. Based on the pharmacophore model, we obtained a five-featured hypothesis AADRR, with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic rings. An atom-based 3D-QSAR model was predicted for 36 training set (R2 = 0.9475, SD = 0.1927, F = 99.3) and nine test set (Q2 = 0.6519, RMSE = 0.4044, Pearson R = 0.834) compounds using pharmacophore-based alignment. From these results, AADRR pharmacophore feature was chosen as the best common pharmacophore hypothesis, whereas the atom-based 3D-QSAR results explain the importance of hydrophobic and electron-withdrawing features for the most active compound 32. The dataset molecules were docked into the active site of Plk1, which shows acceptable hydrogen bond interactions with residues Cys133, Asp194, Glu131, Lys82 & Glu140 and also shows further hydrogen bond interactions with hydrophobic residues Cys67, Leu59 and Arg136. These results can be helpful for further design of novel Plk1 inhibitors.
    Journal of Saudi Chemical Society 04/2014; 12. DOI:10.1016/j.jscs.2014.03.007 · 2.52 Impact Factor
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    • "Consequently, the phosphorylation of overexpressed Plk1 biosensor could mostly reflect the progressive accumulation of Plk1 kinase itself during S/G2 progression exhibiting a basal activity rather than its activation process during G2 to mitosis progression. Nevertheless, it should be noticed that the activation kinetics reported by the Plk1 biosensor agree with recent publications suggesting a role of Plk1 during DNA replication (reviewed in [36]). Further investigations will be required to determine precisely when and where Plk1 activation by Aurora-A is taking place during G2 phase progression. "
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    ABSTRACT: Mitosis has been studied since the early 1880s as a key event of the cell division cycle where remarkable changes in cellular architecture take place and ultimately lead to an equal segregation of duplicated chromosomes into two daughter cells. A detailed description of the complex and highly ordered cellular events taking place is now available. Many regulators involved in key steps including entry into mitosis, nuclear envelope breakdown, microtubule (MT) spindle formation, and chromosome attachment, as well as mitotic exit and cytokinesis, have also been identified. However, understanding the precise spatio-temporal contribution of each regulator in the cell reorganization process has been technically challenging. This review will focus on a number of recent advances in our understanding of the spatial distribution of protein activities and the temporal regulation of their activation and inactivation during entry and progression through mitosis by the use of intramolecular Förster resonance energy transfer (FRET)-based biosensors.
    Biotechnology Journal 02/2014; 9(2). DOI:10.1002/biot.201300194 · 3.49 Impact Factor
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