Regulation of Cell Functions
Enrique Pimentel in Handbook of Growth Factors, 2017
The cell cycle comprises four major phases: G1, S (DNA synthesis period), G2, and M (mitosis period).31,32 The phases of the cell cycle are schematically represented in Figure 1.2. The S phase corresponds to the period of DNA replication, a process that depends on the activity of several types of DNA polymerases,33 as well as on the activity of other enzymes and factors. G1 is the gap period between M and the initiation of DNA synthesis, and G2 is the period between S and M. Cells in G2 contain double the amount of DNA than cells in G1. For most cells growing exponentially in culture, the interval between cell divisions is between 10 and 30 h. Differences in the duration of the cycle between different types of cells or different environmental conditions are mainly due to variation in the length of G1, with the duration of S (6 to 8 h) + G2 (2 to 6 h) + M (1 h) being relatively constant. In addition, there is much variability in the length of G1 among individual cells in a single population. Animal cells, both in vivo and in vitro, can also exist in a nongrowing, quiescent state during which they do not divide for long periods. Most frequently, normal cells that have ceased to grow have the G1 content of DNA. Quiescent cells may be metabolically different from cycling G1 cells and are considered to be in a distinct state, termed G0.
Antineoplastic Agents
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Figure 21.1 illustrates the four successive phases of the cell cycle. Normal, proliferating somatic cells spend the majority of their existence in interphase. Cells also perform most of their maintenance functions in interphase. As a cell prepares to divide, it enters the G1 phase, the period between mitosis (M phase) and DNA synthesis (S phase). The G1 phase lasts from several hours to days and is characterized by synthesis of cell organelles and centriole replication (the G0 phase represents a resting stage or sub-phase of G1). The S phase begins when DNA synthesis starts and the chromosomes have replicated. The G2 phase starts when DNA replication is complete and the content of the nucleus has doubled. The G2phase ends when mitosis starts. The extended part of interphase then continues in the M phase with the stages of cell division— prophase, metaphase, anaphase, and telophase. During this time, the M phase begins with mitosis (nuclear division) and ends with cytokinesis (cytoplasmic) division. Cell division terminates with the completion of cytokinesis.
Introduction to Blood Cancers
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
In order to understand how the natural cycle of the cells is perturbed by the acquisition of the various cancer-specific abnormalities in activating the stimulatory genes (oncogenes) and the inhibitory genes (tumor suppressor), we should understand the phases through which a cell passes as it divides. The cell cycle, shown schematically in Fig. 1.9, consists of four well-characterized stages (or phases), which are defined biochemically, morphologically, and on the basis of the cellular DNA content. During the first stage, known as the G1 phase (where G1 stands for gap 1), the cell increases in size and prepares to duplicate its DNA, which will occur in the second stage, known as the S phase (where S stands for synthesis). During the S phase, the cellular DNA is duplicated on a wholesale scale and a complete copy of the chromosome complement is made. The cell then enters the third stage, termed the G2 phase (where G2 stands for gap 2) during which the cell prepares itself for division.
Enhancing radiosensitisation of BRCA2-proficient and BRCA2-deficient cell lines with hyperthermia and PARP1-i
Published in International Journal of Hyperthermia, 2018
Arlene L. Oei, Vidhula R. Ahire, C. M. van Leeuwen, Rosemarie ten Cate, Lukas J. A. Stalpers, Johannes Crezee, H. Petra Kok, Nicolaas A. P. Franken
DNA is replicated during the S-phase of the cell cycle. Enzyme helicase unzips DNA strands, creating a replication fork, where multiple proteins can bind. These proteins can restore DNA damage thereby preventing genome instability, before DNA replication may proceed [1]. If DNA replication is compromised, DNA damages, such as single strand breaks (SSBs) may occur. One of the proteins that is recruited at sites of stalled forks is Poly(ADP-ribose)polymerase1 (PARP1). Along with other repair proteins, PARP1 binds to the DNA and repairs damages and reinitiates DNA replication at the stalled forks [2]. If PARP1 cannot cope with these SSBs during this semi-conservative repair process, the SSBs can be converted to DNA double strand breaks (DSBs) or also referred to as a double strand end (DSE) [3]. Consequently, this primarily activates homologous recombination (HR) to repair DNA damage in the S- and G2-phases of the cell cycle [4,5]. Thus, as PARP1 is required for regulating replication integrity, interference by PARP1-inhibitors (PARP1-i) gives rise to DSEs caused by failures during DNA replication.
Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mona S. El-Zoghbi, Samiha A. El-Sebaey, Hanan A. AL-Ghulikah, Eman A. Sobh
The cell cycle is required for cell division and replication. The cell cycle was divided into four distinct phases: G1 phase (synthesis), S phase (synthesis), G2 phase (interphase), and M phase (mitosis). The G1 phase, also known as the post-mitotic pre-synthesis phase, is distinguished by direct cell division. DNA replication identifies the S phase. The G2 phase, premitotic, or post-synthetic phase, which can be considered the actual division, is when the cell prepares to split into two cells. Finally, the doubled DNA organised in chromosomes is separated during the M- or mitosis-phase division25. Many anticancer drugs cause apoptosis, cell cycle arrest, or a combination of both as part of their cytotoxic action52. As a result, it was worth investigating whether cell cycle arrest was involved in the cytotoxicity mechanism of the most active cytotoxic agent 4c on A549 cells using flow cytometry analysis, and the results were demonstrated in Table 4 and Figure 7. The results revealed a 69.07% increase in cell count at the G0-G1 phase, compared to 56.39% for control cells. While the percentage of cells in the S phase was reduced by 26.89% compared to the control (29.64%). On the other hand, a dramatic fall in the cell population in the G2/M phase was observed upon treatment with compound 4c from 13.97 to 4.04%. As a result, compound 4c was demonstrated to significantly disrupt the cell cycle profile and cause cell cycle arrest.
Discovery of potent histone deacetylase inhibitors with modified phenanthridine caps
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Wenli Fan, Lin Zhang, Xuejiang Wang, Haiyong Jia, Lei Zhang
The cell cycle is divided into three distinct phases including G0/G1 phase, S phase, and G2/M phase. G2/M is important for the entrance of cells into the M phase. To verify the causal relation of cell proliferation inhibition of Fb-4 and cell cycle arrest, the cell cycle distribution was analysed by treating MCF-7 cells with various doses of Fb-4 and SAHA (1, 3 and 9 µM) for 24 h. As shown in Figure 2, both Fb-4 (Figure 2(A)) and SAHA (Figure 2(B)) increased cell number at G2/M phase with raising concentration, accompanied by decreased cell number at S phase in MCF-7 cells. Compared with SAHA (15.39%, 20.75% and 38.48% at the concentration of 1, 3 and 9 µM, respectively), molecule Fb-4 exhibited significant effects in the G2/M phase arrest of MCF-7 cells with cell percentage of 17.46, 24.81, and 41.71 at the concentration of 1, 3 and 9 µM, respectively. It is demonstrated that treatment of MCF-7 cells with Fb-4 could effectively inhibit cell proliferation via induction of cell cycle arrest at G2/M phase. It is suggested that molecule Fb-4 could inhibit cell proliferation of MCF-7 cells by inhibiting protein synthesis and rapid cell growth as a result of G2/M phase arrest.
Related Knowledge Centers
- Cyclin
- DNA
- DNA Replication
- G1 Phase
- G2 Phase
- Mitogen
- Cell Cycle
- Restriction Point
- Cyclin-Dependent Kinase
- Whi5