Cell cycle. Briefly about interphase

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Human body height is caused by an increase in the size and number of cells, the latter being ensured by the process of division, or mitosis. Cell proliferation occurs under the influence of extracellular growth factors, and the cells themselves undergo a repeating sequence of events known as the cell cycle.

There are four main phases: G1 (presynthetic), S (synthetic), G2 (postsynthetic) and M (mitotic). This is followed by separation of the cytoplasm and plasma membrane, resulting in two identical daughter cells. The phases Gl, S and G2 are part of the interphase. Chromosome replication occurs during the synthetic phase, or S phase.
Majority cells are not subject to active division; their mitotic activity is suppressed during the GO phase, which is part of the G1 phase.

M-phase duration is 30-60 minutes, while the entire cell cycle takes place in about 20 hours. Depending on age, normal (non-tumor) human cells undergo up to 80 mitotic cycles.

Processes cell cycle are controlled by sequentially repeated activation and inactivation of key enzymes called cyclin-dependent protein kinases (CDPKs), as well as their cofactors, cyclins. In this case, under the influence of phosphokinases and phosphatases, phosphorylation and dephosphorylation of special cyclin-CZK complexes occur, which are responsible for the onset of certain phases of the cycle.

In addition, on the relevant stages similar to CZK proteins cause compaction of chromosomes, rupture of the nuclear envelope and reorganization of cytoskeletal microtubules in order to form a fission spindle (mitotic spindle).

G1 phase of the cell cycle

G1 phase- an intermediate stage between the M and S phases, during which the amount of cytoplasm increases. In addition, at the end of the G1 phase there is a first checkpoint where DNA repair and environmental conditions are checked (whether they are favorable enough for the transition to the S phase).

In case nuclear DNA damaged, the activity of the p53 protein increases, which stimulates the transcription of p21. The latter binds to a specific cyclin-CZK complex, responsible for transferring the cell to the S-phase, and inhibits its division at the Gl-phase stage. This allows repair enzymes to repair damaged DNA fragments.

If pathologies occur p53 protein replication of defective DNA continues, which allows dividing cells to accumulate mutations and contributes to the development of tumor processes. This is why the p53 protein is often called the “guardian of the genome.”

G0 phase of the cell cycle

Cell proliferation in mammals is possible only with the participation of cells secreted by other cells. extracellular growth factors, which exert their effect through cascade signal transduction of proto-oncogenes. If during the G1 phase the cell does not receive appropriate signals, then it exits the cell cycle and enters the G0 state, in which it can remain for several years.

The G0 block occurs with the help of proteins - suppressors of mitosis, one of which is retinoblastoma protein(Rb protein) encoded by normal alleles of the retinoblastoma gene. This protein attaches to skew regulatory proteins, blocking the stimulation of transcription of genes necessary for cell proliferation.

Extracellular growth factors destroy the block by activation Gl-specific cyclin-CZK complexes, which phosphorylate the Rb protein and change its conformation, as a result of which the connection with regulatory proteins is broken. At the same time, the latter activate the transcription of the genes they encode, which trigger the process of proliferation.

S phase of the cell cycle

Standard quantity DNA double helices in each cell, the corresponding diploid set of single-stranded chromosomes is usually designated as 2C. The 2C set is maintained throughout the G1 phase and doubles (4C) during the S phase, when new chromosomal DNA is synthesized.

Starting from the end S-phase and until M phase (including G2 phase), each visible chromosome contains two tightly bound DNA molecules called sister chromatids. Thus, in human cells, from the end of the S-phase to the middle of the M-phase, there are 23 pairs of chromosomes (46 visible units), but 4C (92) double helices of nuclear DNA.

In progress mitosis identical sets of chromosomes are distributed among two daughter cells in such a way that each of them contains 23 pairs of 2C DNA molecules. It should be noted that the G1 and G0 phases are the only phases of the cell cycle during which 46 chromosomes in cells correspond to a 2C set of DNA molecules.

G2 phase of the cell cycle

Second check Point, where cell size is tested, is at the end of the G2 phase, located between S phase and mitosis. In addition, at this stage, before moving on to mitosis, the completeness of replication and DNA integrity are checked. Mitosis (M-phase)

1. Prophase. The chromosomes, each consisting of two identical chromatids, begin to condense and become visible inside the nucleus. At the opposite poles of the cell, a spindle-like apparatus begins to form around two centrosomes from tubulin fibers.

2. Prometaphase. The nuclear membrane divides. Kinetochores form around the centromeres of chromosomes. Tubulin fibers penetrate into the nucleus and concentrate near the kinetochores, connecting them with fibers emanating from the centrosomes.

3. Metaphase. The tension of the fibers causes the chromosomes to line up midway between the spindle poles, thereby forming the metaphase plate.

4. Anaphase. Centromere DNA, shared between sister chromatids, is duplicated, and the chromatids separate and move apart closer to the poles.

5. Telophase. The separated sister chromatids (which from this point on are considered chromosomes) reach the poles. A nuclear membrane appears around each group. The compacted chromatin dissipates and nucleoli form.

6. Cytokinesis. The cell membrane contracts and a cleavage furrow is formed in the middle between the poles, which over time separates the two daughter cells.

Centrosome cycle

In G1 phase time a pair of centrioles linked to each centrosome separates. During the S and G2 phases, a new daughter centriole is formed to the right of the old centrioles. At the beginning of the M phase, the centrosome divides, and two daughter centrosomes move toward the cell poles.

The cell cycle is the period of cell existence from the moment of its formation by dividing the mother cell until its own division or death.

Cell cycle duration

The length of the cell cycle varies among different cells. Rapidly reproducing cells of adult organisms, such as hematopoietic or basal cells of the epidermis and small intestine, can enter the cell cycle every 12-36 hours. Short cell cycles (about 30 minutes) are observed during rapid fragmentation of eggs of echinoderms, amphibians and other animals. Under experimental conditions, many cell culture lines have a short cell cycle (about 20 hours). For most actively dividing cells, the period between mitoses is approximately 10-24 hours.

Cell cycle phases

The eukaryotic cell cycle consists of two periods:

A period of cell growth called “interphase,” during which DNA and proteins are synthesized and preparation for cell division occurs.

The period of cell division, called “phase M” (from the word mitosis - mitosis).

Interphase consists of several periods:

G 1-phase (from English. gap- interval), or the initial growth phase, during which the synthesis of mRNA, proteins, and other cellular components occurs;

S-phase (from English. synthesis- synthesis), during which DNA replication of the cell nucleus occurs, doubling of centrioles also occurs (if they exist, of course).

G 2 phase, during which preparation for mitosis occurs.

In differentiated cells that no longer divide, there may be no G 1 phase in the cell cycle. Such cells are in the resting phase G0.

The period of cell division (phase M) includes two stages:

karyokinesis (division of the cell nucleus);

cytokinesis (cytoplasm division).

In turn, mitosis is divided into five stages.

The description of cell division is based on light microscopy data in combination with microcine photography and on the results of light and electron microscopy of fixed and stained cells.

Cell cycle regulation

The regular sequence of changes in periods of the cell cycle occurs through the interaction of proteins such as cyclin-dependent kinases and cyclins. Cells in the G0 phase can enter the cell cycle when exposed to growth factors. Various growth factors, such as platelet-derived, epidermal, and nerve growth factors, by binding to their receptors, trigger an intracellular signaling cascade, ultimately leading to the transcription of cyclin genes and cyclin-dependent kinases. Cyclin-dependent kinases become active only when interacting with the corresponding cyclins. The content of various cyclins in the cell changes throughout the cell cycle. Cyclin is a regulatory component of the cyclin-cyclin-dependent kinase complex. The kinase is the catalytic component of this complex. Kinases are not active without cyclins. Different cyclins are synthesized at different stages of the cell cycle. Thus, the content of cyclin B in frog oocytes reaches a maximum at the time of mitosis, when the entire cascade of phosphorylation reactions catalyzed by the cyclin B/cyclin-dependent kinase complex is launched. By the end of mitosis, cyclin is rapidly destroyed by proteinases.

InterphaseG1 follows the telophase of mitosis. During this phase, the cell synthesizes RNA and proteins. The duration of the phase is from several hours to several days. G0. Cells may exit the cycle and be in the G0 phase. In the G0 phase, cells begin to differentiate. S. During the S phase, protein synthesis continues in the cell, DNA replication occurs, and centrioles separate. In most cells, the S phase lasts 8-12 hours. G2. During the G2 phase, RNA and protein synthesis continues (for example, the synthesis of tubulin for mitotic spindle microtubules). Daughter centrioles reach the size of definitive organelles. This phase lasts 2-4 hours. Mitosis During mitosis, the nucleus (karyokinesis) and cytoplasm (cytokinesis) divide. Phases of mitosis: prophase, prometaphase, metaphase, anaphase, telophase (Fig. 2-52). Prophase. Each chromosome consists of two sister chromatids connected by a centromere; the nucleolus disappears. Centrioles organize the mitotic spindle. A pair of centrioles is part of the mi-

Rice. 2-51. Stages of the cell cycle. The cell cycle is divided into mitosis, a relatively short phase M, and a longer period, interphase. Phase M consists of prophase, prometaphase, metaphase, anaphase and telophase; interphase consists of phases Gj, S and G2. Cells leaving the cycle no longer divide and begin to differentiate. Cells in G0 phase usually do not cycle back. Rice. 2-52. M phase of the cell cycle. After the G2 phase, the M phase of the cell cycle begins. It consists of five stages of nuclear division (karyokinesis) and cytoplasmic division (cytokinesis). The M phase ends at the beginning of the G1 phase of the next cycle. otic center from which microtubules extend radially. First, the mitotic centers are located near the nuclear membrane, and then they diverge and a bipolar mitotic spindle is formed. This process involves pole microtubules, which interact with each other as they elongate. Centriole is part of the centrosome (the centrosome contains two centrioles and a pericentriole matrix) and has the shape of a cylinder with a diameter of 150 nm and a length of 500 nm; the cylinder wall consists of 9 triplets of microtubules. In the centrosome, the centrioles are located at right angles to each other. During the S phase of the cell cycle, centrioles are duplicated. In mitosis, pairs of centrioles, each consisting of an original and a newly formed one, diverge to the cell poles and participate in the formation of the mitotic spindle. Prometaphase. The nuclear envelope disintegrates into small fragments. In the centromere region, kinetochores appear, functioning as centers for organizing kinetochore microtubules. The departure of kinetochores from each chromosome in both directions and their interaction with the polar microtubules of the mitotic spindle is the reason for the movement of chromosomes.

Metaphase. Chromosomes are located in the equator region of the spindle. A metaphase plate is formed in which each chromosome is held by a pair of kinetochores and associated kinetochore microtubules directed to opposite poles of the mitotic spindle. Anaphase— divergence of daughter chromosomes to the poles of the mitotic spindle at a speed of 1 μm/min. Telophase. The chromatids approach the poles, the kinetochore microtubules disappear, and the pole ones continue to elongate. The nuclear envelope is formed and the nucleolus appears. Cytokinesis- division of the cytoplasm into two separate parts. The process begins in late anaphase or telophase. The plasmalemma is retracted between the two daughter nuclei in a plane perpendicular to the long axis of the spindle. The cleavage furrow deepens, and a bridge remains between the daughter cells - a residual body. Further destruction of this structure leads to complete separation of daughter cells. Regulators of cell division Cell proliferation, which occurs through mitosis, is tightly regulated by a variety of molecular signals. The coordinated activity of these multiple cell cycle regulators ensures both the transition of cells from phase to phase of the cell cycle and the precise execution of the events of each phase. The main reason for the appearance of proliferatively uncontrolled cells is mutations in genes encoding the structure of cell cycle regulators. Regulators of the cell cycle and mitosis are divided into intracellular and intercellular. Intracellular molecular signals are numerous, among them, first of all, cell cycle regulators themselves (cyclins, cyclin-dependent protein kinases, their activators and inhibitors) and tumor suppressors should be mentioned. Meiosis During meiosis, haploid gametes are formed (Fig. 2-53, see also

rice. 15-8). First meiotic division The first division of meiosis (prophase I, metaphase I, anaphase I and telophase I) is reduction. Prophase I goes through several stages successively (leptotene, zygotene, pachytene, diplotene, diakinesis). Leptotene- chromatin condenses, each chromosome consists of two chromatids connected by a centromere. Rice. 2-53. Meiosis ensures the transition of germ cells from a diploid state to a haploid state. Zygotene- homologous paired chromosomes come closer and come into physical contact (synapsis) in the form of a synaptonemal complex that ensures the conjugation of chromosomes. At this stage, two adjacent pairs of chromosomes form a bivalent. Pachytena- chromosomes thicken due to spiralization. Separate sections of conjugated chromosomes intersect with each other and form chiasmata. Happening here crossing over- exchange of sections between paternal and maternal homologous chromosomes. Diplotena- separation of conjugated chromosomes in each pair as a result of longitudinal cleavage of the synaptonemal complex. The chromosomes are split along the entire length of the complex, with the exception of the chiasmata. Within the bivalent, 4 chromatids are clearly distinguishable. Such a bivalent is called a tetrad. Unwinding sites appear in the chromatids where RNA is synthesized. Diakinesis. The processes of chromosome shortening and splitting of chromosome pairs continue. Chiasmata move to the ends of chromosomes (terminalization). The nuclear membrane is destroyed and the nucleolus disappears. The mitotic spindle appears. Metaphase I. In metaphase I, the tetrads form the metaphase plate. In general, paternal and maternal chromosomes are randomly distributed on one side or the other of the equator of the mitotic spindle. This pattern of chromosome distribution underlies Mendel's second law, which (along with crossing over) ensures genetic differences between individuals.

1. What is the cell cycle?

The cell cycle is the existence of a cell from the moment of its formation during the division of the mother cell until its own division (including this division) or death. The cell cycle consists of interphase and mitosis (cell division).

2. What is called interphase? What main events occur in the G 1 -, S- and G 2 -periods of interphase?

Interphase is the part of the cell cycle between two successive divisions. During the entire interphase, chromosomes are non-spiralized and are located in the cell nucleus in the form of chromatin. As a rule, interphase consists of three periods:

● Presynthetic period (G 1) – the longest part of the interphase (from 2 – 3 hours to several days). During this period, the cell grows, the number of organelles increases, energy and substances are accumulated for the subsequent doubling of DNA. During the G 1 period, each chromosome consists of one chromatid. The set of chromosomes (n) and chromatids (c) of a diploid cell in the G 1 period is 2n2c.

● During the synthetic period (S), DNA doubling (replication) occurs, as well as the synthesis of proteins necessary for the subsequent formation of chromosomes. During this same period, the doubling of centrioles occurs. By the end of the S period, each chromosome consists of two identical sister chromatids connected at the centromere. The set of chromosomes and chromatids of a diploid cell at the end of the S-period (i.e. after replication) is 2n4c.

● During the postsynthetic period (G 2), the cell accumulates energy and synthesizes proteins for the upcoming division (for example, tubulin to build microtubules, which subsequently form the spindle). During the entire G 2 period, the set of chromosomes and chromatids in the cell is 2n4c.

At the end of interphase, cell division begins.

3. Which cells are characterized by the G 0 period? What happens during this period?

Unlike constantly dividing cells (for example, cells of the germinal layer of the epidermis of the skin, red bone marrow, the mucous membrane of the gastrointestinal tract of animals, cells of the educational tissue of plants), most cells of a multicellular organism take the path of specialization and, after passing through part of the G 1 period, pass during the rest period (G 0 -period).

Cells in the G0 period perform their specific functions in the body; metabolic and energy processes occur in them, but preparation for replication does not occur. Such cells, as a rule, permanently lose their ability to divide. Examples include neurons, lens cells, and many others.

However, some cells that are in the G0 period (for example, leukocytes, liver cells) can leave it and continue the cell cycle, going through all periods of interphase and mitosis. Thus, liver cells can again acquire the ability to divide after several months of being in a period of rest.

4. How is DNA replication carried out?

Replication is the duplication of DNA, one of the reactions of template synthesis. During replication, special enzymes separate the two strands of the original parent DNA molecule, breaking the hydrogen bonds between complementary nucleotides. Molecules of DNA polymerase, the main replication enzyme, bind to the separated strands. Then the DNA polymerase molecules begin to move along the mother chains, using them as templates, and synthesize new daughter chains, selecting nucleotides for them according to the principle of complementarity.

As a result of replication, two identical double-stranded DNA molecules are formed. Each of them contains one chain of the original mother molecule and one newly synthesized daughter chain.

5. Are the DNA molecules that make up homologous chromosomes the same? In the composition of sister chromatids? Why?

DNA molecules in sister chromatids of one chromosome are identical (have the same nucleotide sequence), because they are formed as a result of replication of the original mother DNA molecule. Each of the two DNA molecules that make up sister chromatids contains one strand of the original mother DNA molecule (template) and one new, daughter strand synthesized on this template.

The DNA molecules in homologous chromosomes are not identical. This is due to the fact that homologous chromosomes have different origins. In each pair of homologous chromosomes, one is maternal (inherited from the mother), and the other is paternal (inherited from the father).

6. What is necrosis? Apoptosis? What are the similarities and differences between necrosis and apoptosis?

Necrosis is the death of cells and tissues in a living organism, caused by the action of damaging factors of various natures.

Apoptosis is programmed cell death regulated by the body (so-called “cellular suicide”).

Similarities:

● Necrosis and apoptosis are two types of cell death.

● Occurs at all stages of the body’s life.

Differences:

● Necrosis is random (unplanned) cell death, which may be caused by exposure to high and low temperatures, ionizing radiation, various chemicals (including toxins), mechanical damage, impaired blood supply or innervation of tissues, or an allergic reaction. Apoptosis is initially planned by the body (genetically programmed) and regulated by it. During apoptosis, cells die without direct damage, as a result of their receiving a specific molecular signal - an “order to self-destruct.”

● As a result of apoptosis, individual specific cells die (only those that have received the “order”), and entire groups of cells usually undergo necrotic death.

● During necrotic death in damaged cells, membrane permeability is disrupted, protein synthesis stops, other metabolic processes stop, the nucleus, organelles and, finally, the entire cell are destroyed. Typically, dying cells are attacked by leukocytes, and an inflammatory reaction develops in the area of necrosis. During apoptosis, the cell breaks up into separate fragments surrounded by plasmalemma. Typically, fragments of dead cells are absorbed by white blood cells or neighboring cells without triggering an inflammatory response.

And (or) other significant features.

7. What is the significance of programmed cell death in the life of multicellular organisms?

One of the main functions of apoptosis in a multicellular organism is to ensure cellular homeostasis. Thanks to apoptosis, the correct ratio of the number of cells of different types is maintained, tissue renewal is ensured, and genetically defective cells are removed. Apoptosis seems to interrupt the infinity of cell divisions. Weakening of apoptosis often leads to the development of malignant tumors and autoimmune diseases (pathological processes in which an immune reaction develops against the body’s own cells and tissues).

8. Why do you think that in the vast majority of living organisms the main keeper of hereditary information is DNA, and RNA performs only auxiliary functions?

The double-stranded nature of the DNA molecule underlies the processes of its self-duplication (replication) and the elimination of damage - repair (the undamaged strand serves as a matrix for restoring the damaged strand). Being single-stranded, RNA is not capable of replication, and its repair processes are hampered. In addition, the presence of an additional hydroxyl group on ribose (compared to deoxyribose) makes RNA more susceptible to hydrolysis than DNA.

What is interphase? The term comes from the Latin word "inter", translated as "between", and the Greek "phasis" - period. This is the most important period during which the cell grows and accumulates nutrients in preparation for the next division. Interphase occupies a large part of the entire cell cycle; up to 90% of the entire life of the cell occurs in it.

What is interphase

As a rule, the main part of the cell components grows throughout the entire phase, so it is quite difficult to distinguish any individual stages in it. Nevertheless, biologists have divided interphase into three parts, focusing on the time of replication in the cell nucleus.

Interphase periods: G(1) phase, S phase, G(2) phase. The presynthetic period (G1), whose name comes from the English gap, translated as “interval,” begins immediately after division. This is a very long period, lasting from ten hours to several days. It is during this period that accumulation of substances occurs and preparation for the doubling of genetic material occurs: RNA synthesis begins and the necessary proteins are formed.

What is interphase in its last period? In the presynthetic phase, the number of ribosomes increases, the surface area of the rough endoplasmic reticulum increases, and new mitochondria appear. The cell, consuming a lot of energy, grows quickly.

Differentiated cells, no longer able to divide, remain in a resting phase called G0.

Main period of interphase

Regardless of what processes occur in the cell during interphase, each of the subphases is important for the overall preparation for mitosis. However, the synthetic period can be called a turning point, because it is during it that chromosomes are doubled and immediate preparation for division begins. RNA continues to be synthesized, but immediately combines with chromosome proteins, beginning DNA replication.

The interphase of the cell in this part lasts from six to ten hours. As a result, each chromosome doubles and already consists of a pair of sister chromatids, which then disperse to the poles of the spindle. In the synthetic phase, centrioles double, if, of course, they are present in the cell. During this period, chromosomes can be seen under a microscope.

Third period

Genetically, the chromatids are absolutely identical, since one of them is maternal, and the second is replicated using messenger RNA.

As soon as complete doubling of all genetic material has occurred, the post-synthetic period begins, preceding division. This is followed by the formation of microtubules, from which the spindle will subsequently form, and the chromatids will diverge to the poles. Energy is also stored, because during mitosis the synthesis of nutrients decreases. The duration of the postsynthetic period is short, usually lasting only a few hours.

Checkpoints

During this process, the cell must pass through certain checkpoints - important “markers”, after which it passes to another stage. If for some reason the cell was unable to pass the checkpoint, then the entire cell cycle freezes, and the next phase will not begin until the problems that prevented it from passing through the checkpoint are corrected.

There are four main points, most of which are just in interphase. The cell passes the first checkpoint in the presynthetic phase, when DNA integrity is checked. If everything is correct, then the synthetic period begins. In it, the point of reconciliation is the verification of accuracy in DNA replication. The checkpoint in the post-synthesis phase is a check for damage or omissions at the two previous points. This phase also checks how completely replication and cells have occurred. Those who do not pass this test are not allowed to participate in mitosis.

Problems in interphase

Disruption of the normal cell cycle can lead not only to failures in mitosis, but also to the formation of solid tumors. Moreover, this is one of the main reasons for their appearance. The normal course of each phase, no matter how short it may be, predetermines the successful completion of subsequent stages and the absence of problems. Tumor cells have changes at cell cycle checkpoints.

For example, in a cell with damaged DNA, the synthetic period of interphase does not occur. Mutations occur that result in loss or changes in the p53 protein genes. There is no blockage of the cell cycle in the cells, and mitosis begins ahead of schedule. The result of such problems is a large number of mutant cells, most of which are non-viable. However, those that can function give rise to malignant cells, which can divide very quickly due to a shortened or absent resting phase. The characteristic of interphase allows malignant tumors consisting of mutant cells to divide so rapidly.

Interphase duration

Let's give a few examples of how much longer the interphase period takes in the life of a cell compared to mitosis. In the epithelium of the small intestine of ordinary mice, the “resting phase” takes at least twelve hours, and mitosis itself lasts from 30 minutes to an hour. The cells that make up the root of faba beans divide every 25 hours, with the M phase (mitosis) lasting about half an hour.

What is interphase for cell life? This is the most important period, without which not only mitosis, but also cellular life as a whole would be impossible.