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The Cell and Cell Division
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
In part, this process is controlled by the synthesis and degradation of the cyclins, but it is also affected by phosphorylation of the CDK on two sites (Fig. 22), which is controlled by two phosphatases known as Wee1 and MO15. Removal of one of the phosphate residues by means of another phosphatase—Cdc25— is then needed for activation of MPF. It is thought that the MPF autocatalytically activates itself, resulting in a steady rise in MPF levels during the cell cycle until the critical point when an explosive increase in activity takes place and drives the cell irretrievably into the M phase. Cdc2 is associated with the G1/S, and the G2/M transitions and cdc4 and cdc6 are associated with start, but are bound to different cyclins (cyclin B at mitosis and cyclin E and A at start at G1/S). The Kip/cip family of cyclin-dependent kinases, which include p21, p27 and p57, are capable of binding to and inhibiting most cyclin/CDK complexes. The expression of these CDK inhibitors is often dependent on upstream events that are activated by physiological signals, such as DNA damage, serum deprivation, or contact inhibition. In contrast, the INK4 family of CDK inhibitors, including p15, p16, p18, and p19, bind to and inactivate D-type cyclins.
Introduction to Molecular Biology
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Although knowledge of the structure of the replication machinery in eukaryotes is still limited due to its complexity, there are many similarities with the simpler prokaryotes DNA replication process. In eukaryotic cells, DNA exists in the nucleus as a very compact and condensed structure. In order to begin the replication process, this structure must be opened up, so the DNA polymerase enzyme can copy the DNA template. The replication process takes place at a specific site called origin of replication, which is rich in AT content. The first step in DNA replication begins with the binding of the origin recognition complex (ORC) to the origin of replication. ORC complex is a hexamer of related proteins that function as a replication initiation factor that promotes the unwinding or denaturation of DNA. Following the binding of the ORC complex, other proteins (Cdc6/Cdc18 and Cdt1) will bind and coordinate the recruitment of the minichromosome maintenance function (MCM) complex to the origin of replication. The MCM complex is a hexamer and is thought to be the major DNA helicase in eukaryotic organisms. Once the binding of MCM occurs, a fully licensed pre-initiation replication complex (pre-RC) now exists. This process occurs during the G1 phase of the cell cycle and therefore, cannot initiate the replication. Replication only occurs during the S phase. Thus, separating the licensing and activation is a mechanism that ensures only one replication per origin in a cell cycle.
Adverse outcome pathways and linkages to transcriptomic effects relevant to ionizing radiation injury
Published in International Journal of Radiation Biology, 2022
Jihang Yu, Wangshu Tu, Andrea Payne, Chris Rudyk, Sarita Cuadros Sanchez, Saadia Khilji, Premkumari Kumarathasan, Sanjeena Subedi, Brittany Haley, Alicia Wong, Catalina Anghel, Yi Wang, Vinita Chauhan
Among the genes that were identified to be differentially expressed across different datasets, 61 and 24 genes available in GEO datasets were used for the development of the network for high- and moderate doses, respectively, using GeneMANIA (Supplementary Table 6). Among these genes, we note that some common genes were found within several AEs. One example is the TP53 gene (encoding P53 protein, a tumor suppressor) that is associated with six AEs, including cell cycle, DNA repair, immune system responses, TP53-mediated transcriptional regulation, cellular responses to stimuli, and disease. We also note that some genes had bi-directional connectivity using GeneMANIA. For example, the proteins encoded by the identified genes involved in DNA replication and cell cycle can regulate each other, such as MCM4 regulates CDC45L, and CDC6 regulates MCM2 (Figures 3 and 4). These specific genes and their corresponding proteins may act as modulators to AEs and are therefore valuable in developing strategies for preventing disease progression.
LncRNA NORAD engages in psoriasis by binding to miR-26a to regulate keratinocyte proliferation
Published in Autoimmunity, 2021
Shuiqi Li, Xiaohua Zhu, Na Zhang, Ruixiang Cao, Lei Zhao, Xin Li, Jiang’an Zhang, Jianbin Yu
Cell division cycle 6 (CDC6) is a promoter of DNA replication and induces keratinocyte proliferation. Sun et al. [7] demonstrated that CDC6 was significantly upregulated in psoriatic skin. A similar result in our experiments showed that CDC6 was elevated accompanied by increased keratinocyte proliferation both in vitro and in vivo, indicated that the decrease of CDC6 and keratinocyte proliferation might be the target of improving the development of psoriasis. Besides, CDC6 expression was decreased in IL-22/LPS-stimulated HaCaT cell model after transfected with si-NORAD. We also determined the interaction between miR-26a and CDC6, which proved that miR-26a negatively regulated the expression of CDC6.