What Is the Connection Between the Cell Cycle and Cancer?

The cell cycle refers to the whole process that a cell goes through from the completion of one division to the end of the next division, and is divided into two phases: interphase and division.

Life is a continuous process that is passed from one generation to the next, so it is a process that is constantly updated and started from scratch. A cell's life begins with the division of the mother cell that produced it, ends with the formation of its daughter cells, or the cell's own death. The formation of daughter cells is usually used as a sign of the end of a cell division. The cell cycle refers to the process from the beginning of a cell division to the formation of a daughter cell to the next cell division to form a daughter cell. In this process, the cell's genetic material is replicated and distributed equally to the two daughter cells.

Chinese name: cell cycle
Foreign name: cell cycle

Definition: The process of continuous cell division into daughter cells
Stage: Interphase

Cell cycle process

Pericellular period

The interphase is divided into three phases, namely, the early DNA synthesis phase (G1 phase), the DNA synthesis phase (S phase), and the late DNA synthesis phase (G2 phase).

1. G1 phase (first gap) The period from mitosis to DNA replication, also known as the pre-synthesis phase. This phase mainly synthesizes RNA and ribosomes. This period is characterized by active material metabolism, rapid synthesis of RNA and protein, and significant increase in cell volume. The main significance of this phase is to prepare material and energy for DNA replication in the next phase S.

2.S phase (synthesis) is the DNA synthesis phase. In this phase, in addition to DNA synthesis, histones are also synthesized. The enzymes required for DNA replication are synthesized during this period.

3. The G2 phase (second gap) is the late stage of DNA synthesis and is the preparation period for mitosis. During this period, DNA synthesis ceased, and a large number of RNA and proteins were synthesized, including tubulin and maturation factors.

Cell cycle division

M phase: cell division phase.

The mitosis of a cell needs to go through anterior, middle, posterior, and terminal stages. It is a continuous process of change from a mother cell to two daughter cells. It usually takes 1 to 2 hours.

1. The prophase chromatin filaments are highly spiralled and gradually form chromosome. The chromosomes are short and thick, and strongly basophilic. The two centrosomes move in opposite directions to form poles in the cell; then, starting from the centrosome satellite as a starting point, microtubules are synthesized to form a spindle. The nucleoli gradually disappears with the helical helical spiraling. The nuclear envelope began to disintegrate into discrete vesicular endoplasmic reticulum.

2. Metaphase cells become spherical, and the nucleoli and nuclear envelope have completely disappeared. The chromosomes are all moved to the equatorial plane of the cell, and the microtubules emitted from the poles of the spindle are attached to the centromere of each chromosome. A total of 46 chromosomes can be isolated from metaphase cells, of which 44 are autosomes and 2 are sex chromosomes. The male karyotype is 44 + XY and the female is 44 + XX. The separated chromosomes are short thick sticks or hairpins, and are composed of two chromatids connected by narrow centromeres.

3 In the later period (anaphase), due to the movement of the spindle microtubules, the centromere is split longitudinally, the two chromatids of each chromosome are separated and moved in opposite directions, close to their respective central bodies, and the chromatids are then divided into two groups. At the same time, the cells were elongated, and due to the movement of the microfilament bundles that circulated under the cell membrane of the equatorial part, the part narrowed and the cells became dumbbell-shaped.

4 The terminal (telophase) chromatid gradually untwisted, and chromatin filaments and nucleoli reappear; the endoplasmic reticulum vesicles combined into a nuclear envelope; the hermaphroditic narrowed and deepened, and finally divided into two diploid daughter cells .

The process that mitotic cells undergo from the end of one division to the end of the next division. This process starts and ends. The cell cycle was one of the major discoveries in cytology in the 1950s. Previously, the mitotic phase was considered to be the main phase in the cell proliferation cycle, and the cells in the interphase were regarded as the stationary phase of the cells . In 1951, Howard et al. Labeled P. faba root tip cells with P-phosphate, and studied the time interval of DNA synthesis in root tip cells by autoradiography. It was observed that the incorporation of P was not in the mitotic phase, but in the period before mitosis in a period of time. It was found that there was a DNA synthesis phase (S phase) during the interphase, and P was only incorporated into the DNA at this time; there was a gap between the S phase and the cleavage phase (M phase) without P incorporation, which was called G2 phase. There is another gap between the M and S phases called the G1 phase, and the G1 phase cannot synthesize DNA.

Most of the life of the cells is spent in interphases, such as in the cell cycle of rat corneal epithelial cells, the interphase takes 14000 minutes. The division period only takes 70 minutes. There are complex biochemical changes at each stage of the cell cycle. Interphase is the period during which cells synthesize DNA, RNA, proteins, and various enzymes. It is the main phase in preparing the material basis for cell division.

In a proliferating cell population, all cells are not proliferating simultaneously. They may have four destinies in the cell cycle:

The cell begins the second cycle through the M phase;

Stop in G2 phase, called G2 phase cell (R2), it can enter the cycle after some kind of stimulation;

Stop in G1 phase, which is called resting cell or G ₀ phase cell. Such cells can enter the cycle after some stimulation, and continue to undergo mitosis;

Cells that lose their vitality and are near death are called lost cells, or cells that are no longer dividing. Cells that continue to divide follow the cell cycle from one mitotic phase to the next. Cells that are no longer dividing leave the cell cycle to no longer divide and eventually die.

G1 Cell cycle G1

Cells gradually increase in size to make RNA (including tRNA, mRNA, rRNA, and ribosomes). RNA synthesis leads to the formation of structural proteins and enzyme proteins, which in turn control the metabolic activities that form new cellular components. G1 is divided into two stages: early G1 and late G1; cells synthesize various RNA and proteins unique to G1 in the early G1 period, and in the late G1 to S phase, they convert to several prerequisites for DNA replication. Body and enzyme molecules, including thymine kinase, thymine nucleotide kinase, deoxythymine nucleotide synthetase, etc., especially DNA polymerases have increased dramatically. The increase in the activity of these enzymes is an essential condition for making full use of nucleic acid substrates to synthesize DNA in the S phase.

cell cycle The duration of the G1 phase varies widely, and the G1 phase of most cells is longer, which is related to the need for cell mass. However, in some unicellular organisms such as Amoeba, Tetrahymena, and certain cells of multicellular organisms (such as sea urchin embryos and mouse embryo cells), there is no G1 phase, and variants of Chinese hamster ovary cells do not have G1 and G2 phases. So that the M and S phases are connected together. The reason why the length of the G1 period varies greatly is related to the existence of a correction point or a blocking point (R point for short) during the G1 period. Point R mainly controls the length of the G1 period. By this point, cells can complete other phases of the cell cycle at a normal rate without being affected by external conditions. Therefore, some people think that the cell growth stops at the R point of the G1 phase. For example, when the intracellular cyclic adenylate (cAMP) level increases and the cell density increases, the cell can be prevented from transitioning from the G1 phase to the S phase. Inhibition of protein synthesis by RNA or radiosporin D can also delay cells from G1 to S phase. Some people find that a triggering protein can be synthesized during the G1 period; it is unstable and can be easily broken down, so it is called v protein. When the v protein reaches a certain level in G1 cells, the cells can enter the S phase through the R point.

After the cells enter the G1 phase, they do not always enter the next phase to continue to proliferate. At this time, three kinds of cells with different prospects may appear: proliferating cells: these cells can enter the S phase from the G1 phase in time, and Maintain a strong ability to divide. For example, gastrointestinal epithelial cells and bone marrow cells; temporarily non-proliferating cells or resting cells: these cells do not immediately switch to the S phase after entering the G1 phase, and enter the S phase to continue proliferation when needed, such as injury or surgery. For example, hepatocytes and renal tubular epithelial cells, etc .; Non-proliferating cells: After entering the G1 phase, these cells lose the ability to divide, stay in the G1 phase for life, and finally undergo differentiation, aging, and death. Such as highly differentiated nerve cells, muscle cells and mature red blood cells.

G0 G0 phase

The regulation of the cell cycle is mainly achieved by the retention of the G1 phase, which means that the cells are in a state of retention. Cells are divided into two by the M phase, and some can continue to divide to cycle, and some can be transferred to the G0 phase. The G0 phase is a phase in which the division of the cell cycle temporarily stops dividing. But under certain suitable stimulation, it can enter the cycle again (Figure 1), synthesize DNA and divide. The characteristics of G0 phase are: in unstimulated G0 cells, the potential for DNA synthesis and cell division still exists; when G0 cells are stimulated to proliferate, they can synthesize DNA and perform cell division.

S Cell cycle S phase

At this stage, DNA synthesis and histones related to DNA assembly and chromatin are completed. The DNA content doubled during this period. At the end of the S phase, each chromosome replicates into two chromatids (Hole, 1979). The resulting two offspring DNA molecules have exactly the same structure as the original DNA molecule. The diameter of a human cell nucleus is 10-20 microns, and the DNA content is 10 grams. If it is pulled into a DNA strand, the length can reach 3 meters. S phase of mammalian cells is generally 6-8 hours. DNA replication can be completed within a few hours, mainly because the DNA strand is divided into many replication units (replicons) (up to about 10,000), which can be replicated at different times in the S phase. In addition, during the S period, there is also the synthesis of histones-histone genes are activated between G1-S phases, and the transcription of histone mRNA increases, and it continues continuously throughout the S phase. The synthesized histones quickly turned the newly synthesized DNA into a nuclear histone complex.

S-phase cells contain a factor that can induce DNA synthesis. Cell fusion experiments have shown that G1 cells can accelerate the start of DNA replication in the nucleus after fusion with S-phase cells. The composition of the DNA bases replicated at different stages of the S phase is different. The DNA that is copied early is rich in GC bases, and the DNA that is copied late is rich in AT bases.

G2 Cell cycle G2

It is the gap between the end of DNA replication and the beginning of mitosis, during which cells synthesize certain proteins and RNA molecules, providing material conditions for entering mitosis. Tracers with radiolabeled RNA precursors and protein precursors indicate a strong RNA and protein synthesis in the G2 phase. If these synthetic processes are disrupted, cells cannot transition to the M phase. G2 synthesizes the components required for chromosome enrichment and formation of the mitotic apparatus. Some people think that the G2 phase continues to complete the synthesis of tubulin from the S phase, providing raw materials for the assembly of the M phase spindle. Synthesis of mitotic factors begins in the late G2. In some cells lacking the G1 phase, the G2 phase is more complicated, and it also bears the events to be completed in the G1 phase of other cells. There are also a few cases where mitosis begins immediately after the end of the S phase, and there is no G2 phase.

M M-phase

The mitosis period is a period of rapid changes in the cell morphology and structure, including a series of changes in the nucleus, the concentration of chromatin, the appearance of the spindle, and the process of the precise and equal distribution of chromosomes into the two daughter cells to keep the cells after division Genetic consistency. The M phase is divided into early, middle, late, and terminal stages (see mitosis). Although the M phase is the period with the most significant morphological changes, its respiratory effect is reduced, protein synthesis is significantly reduced, and RNA synthesis and other metabolic turnover are stopped. This is because the energy and other basic substances required during mitosis are synthesized during the interphase. It's related to being prepared.

During the cell cycle, a series of changes in the cell morphology also occur. From the light microscope, the cells in the G1 phase are the smallest, and the cells are flat and smooth. With the development of the S G2 M phase, the cells gradually increase and change from flat to spherical. . Scanning electron microscope can clearly see the changes in cell surface morphology in various periods, such as microvilli gradually increased, these changes are related to various biochemical and physiological periodic changes in the cell.

Many biochemical events in the regulation of the cell cycle proceed in a certain order and methodically, which is closely related to the expression of genes in a certain order.

Cell cycle influencing factors

There are two stages in the cell cycle that are most important: G1 to S and G2 to M; these two stages are at a period of complex and active molecular level changes, and are easily affected by environmental conditions. If they can be artificially controlled, it will affect the It is important to understand the growth and development of organisms and control tumor growth.

Many in vivo factors have been found to stimulate or inhibit cell proliferation, such as various hormones, serum factors, polyamines, proteolytic enzymes, neuraminidases, cAMP, cGMP and diglycerides (DG), inositol triphosphate (IP3) And Ca messenger system and more. Increased intracellular cAMP concentration can inhibit cell proliferation. All factors that increase intracellular cAMP can inhibit cell proliferation and reduce cell growth rate. Conversely, all factors that can reduce intracellular cAMP content can promote DNA. Synthesis and cell proliferation. The cAMP content is also different in each phase of the cell cycle (see table). Among Chinese hamster ovary cell lines, the cAMP content was the lowest in the M phase, and the cAMP level increased three-fold after the M phase. From early G1 to late G1, cAMP levels decreased to moderate levels, and remained low until S phase (Figure 3) .

Many experiments have pointed out that cGMP also regulates cell proliferation. For example, when cGMP or dibutyryl cGMP is added to 3T3 cells resting in G1 phase, it can induce an increase in DNA content and promote cell division. If cGMP levels are increased, mitosis can be promoted. Conversely, drugs that promote mitosis can also increase cGMP concentrations.

cAMP can inhibit cell division and promote cell differentiation. cGMP can inhibit cell differentiation and promote cell proliferation. In normal growing cells, cAMP and cGMP are maintained at appropriate levels to regulate and control the operation of the cell cycle.

Somatostatin is a small molecule protein or polypeptide produced by cells, and some also contain sugar or RNA. It is non-species-specific, but cell-specific. It has an inhibitory effect on the proliferation of similar cells and is reversible. When the content of inhibin reaches a certain concentration, the proliferation of the same type of cells can be inhibited. When the concentration of inhibin is decreased, the cell proliferation is active. Some people think that the mechanism of statin is that it can activate adenylate cyclase activity on the cell membrane, increase the concentration of cAMP in the cell, and thus inhibit cell proliferation. It may also be through the phosphorylation of protein by cAMP-dependent protein kinase To influence the activity of regulatory genes.

The cell cycle is also affected by the body's regulatory system. For example, liver regeneration is the role of the regulatory system to accelerate liver cell proliferation. However, tumor cells proliferate malignantly because the host loses control of it. The principle of cell cycle can be applied in tumor treatment. For example, G0 cells are not sensitive to chemotherapy and often become the source of cancer recurrence in the future. Therefore, the research of regulatory mechanisms can be used to induce G0 cancer cells to enter the cell cycle and then use anti-cancer reasonably Drug killing is an important regulatory measure to prevent cancer metastasis and spread, and it is a theoretical and practical research issue in cell dynamics.

In short, the molecular basis of cell proliferation regulation that is understood so far is still to be further explored.

Cell cycle cell classification

Cells can be divided into three types according to their ability to divide in the body: Periodic cells, such as hematopoietic stem cells, stem cells of the epidermis and gastrointestinal mucosa. Such cells always maintain an active ability to divide and continue to enter the cell cycle cycle; terminally differentiated cells, such as mammalian mature red blood cells, nerve cells and other highly differentiated cells, which have lost the ability to divide, also known as end cells ); temporarily non-proliferating cell population (G0 phase cells), such as liver cells, renal tubular epithelial cells, cardiac muscle cells, thyroid follicular epithelial cells. They are differentiated and perform specific functions. They are usually in the G0 phase, so they are also called G0 phase cells. Under certain stimuli, these cells reenter the cell cycle. After partial liver resection, the remaining liver cells divide rapidly.

DNA Cell cycle DNA proliferation characteristics

Bacterial DNA replication, RNA transcription, and protein synthesis occur simultaneously, which is why bacteria respond to rapid growth.

DNA replication is not limited by the cell cycle. At the end of the last cell division, the DNA in the cell is replicated to half the process to ensure that the next division can be performed quickly.

1. The cell cycle is the whole process from the beginning of the first division to the beginning of the second division. Chen Yuezeng, General Biology

2. The cell cycle is the whole process from the end of the first division to the end of the second division. "Cell Biology" Qu Zhonghe, Wang Xizhong, Ding Mingxiao

The difference between the two is the origin of cell division. The second argument is generally accepted today.

Cell cycle tips

Take plant cell mitosis as an example:

Mitosis in five segments

Connected in time

Interim preparation

Interphase chromosomes

Disappearance in the previous period

Mid-centromere poly-equatorial plate

Late silk distractor bipolar walk

Reconstruction of the last two eliminations and two existing walls

Note: Animal cells do not develop cell walls at the end.