General characteristics of the interphase nucleus

The nucleus is the most important component of the cell, which is found in almost all cells of multicellular organisms. Most cells have one nucleus, but there are binucleated and multinucleated cells (for example, striated muscle fibers). Dual and multinucleation are due to functional characteristics or pathological state of cells. The shape and size of the nucleus are very variable and depend on the type of organism, type, age and functional state of the cell. On average, the volume of the nucleus is approximately 10% of the total volume of the cell. Most often, the nucleus has a round or oval shape, ranging in size from 3 to 10 microns in diameter. The minimum size of the nucleus is 1 micron (in some protozoa), the maximum is 1 mm (the eggs of some fish and amphibians). In some cases, there is a dependence of the shape of the nucleus on the shape of the cell. The nucleus usually occupies a central position, but in differentiated cells it can be displaced to the peripheral part of the cell. Almost all the DNA of a eukaryotic cell is concentrated in the nucleus.

The main functions of the kernel are:

1) Storage and transmission of genetic information;

2) Regulation of protein synthesis, metabolism and energy in the cell.

Thus, the nucleus is not only a receptacle for genetic material, but also a place where this material functions and reproduces. Therefore, disruption of any of these functions will lead to cell death. All this points to the leading role of nuclear structures in the synthesis of nucleic acids and proteins.

BLAKING

Core. Chromatin, heterochromatin, euchromatin.

The nucleus (lat.nucleus) is one of the structural components of a eukaryotic cell, containing genetic information (DNA molecules), performing the main functions: storage, transmission and implementation of hereditary information with the provision of protein synthesis. The nucleus consists of chromatin, nucleolus, karyoplasm (or nucleoplasm) and nuclear envelope. In the cell nucleus, replication (or reduplication) occurs - the doubling of DNA molecules, as well as transcription - the synthesis of RNA molecules on a DNA molecule. RNA molecules synthesized in the nucleus are modified, after which they enter the cytoplasm. The formation of both ribosome subunits occurs in special formations of the cell nucleus - the nucleoli. Thus, the cell nucleus is not only a repository of genetic information, but also a place where this material functions and reproduces.

The nucleus of a non-dividing, interphase cell is usually one per cell (although multinucleated cells are also found). The nucleus consists of chromatin, nucleolus, karyoplasm (nucleoplasm) and the nuclear envelope separating it from the cytoplasm (Fig. 17).

Chromatin

When observing living or fixed cells inside the nucleus, zones of dense matter are identified, which are well perceived by various dyes, especially basic ones. Due to this ability to stain well, this component of the nucleus is called "chromatin" (from the Greek chroma - color, paint). Chromatin contains DNA in a complex with protein. Chromosomes, which are clearly visible during mitotic cell division, have the same properties. In non-dividing (interphase) cells, chromatin, detected in a light microscope, can more or less uniformly fill the volume of the nucleus or be located in separate lumps.

Chromatin of interphase nuclei is a chromosome, which, however, at this time lose their compact form, loosen, decondensate. The degree of such decondensation of chromosomes can be different. The morphologists call the zones of complete decondensation of their sites euchromatin. With incomplete loosening of chromosomes in the interphase nucleus, areas of condensed chromatin, sometimes called heterochromatinum, are visible. The degree of decondensation of chromosomal material - chromatin in the interphase may reflect the functional load of this structure. The more "diffuse" chromatin is distributed in the interphase nucleus (ie, the more euchromatin), the more intense the synthetic processes in it.

Chromatin is maximally condensed during mitotic cell division, when it is found in the form of dense chromosomes. During this period, the chromosomes do not perform any synthetic functions, and the precursors of DNA and RNA are not included in them.

Thus, the chromosomes of cells can be in two structural and functional states: in active, working, partially or completely decondensed, when with their participation in the interphase nucleus, the processes of transcription and reduplication occur, and in an inactive state, in a state of metabolic rest with their maximum condensation, when they perform the function of distributing and transferring genetic material to daughter cells.

Chromatin

The enormous length of eukaryotic DNA molecules predetermined the emergence of special mechanisms for storage, replication and implementation of genetic material. Chromatin is called a molecule of chromosomal DNA in combination with specific proteins necessary for the implementation of these processes. The bulk is made up of "storage proteins", the so-called histones. From these proteins are built nucleosomes - structures on which the strands of DNA molecules are wound. Nucleosomes are arranged quite regularly, so that the resulting structure resembles a bead. The nucleosome consists of four types of proteins: H2A, H2B, H3, and H4. One nucleosome contains two proteins of each type - a total of eight proteins. Histone H1, which is larger than other histones, binds to DNA where it enters the nucleosome. The nucleosome, together with the H1, is called the chromosome.

A DNA strand with nucleosomes forms an irregular solenoid-like structure about 30 nanometers thick, the so-called 30 nm fibril. Further packing of this fibril can have different densities. If chromatin is tightly packed, it is called condensed or heterochromatin, it is clearly visible under a microscope. The DNA found in heterochromatin is not transcribed, usually this condition is characteristic of insignificant or silent regions. In the interphase, heterochromatin is usually located at the periphery of the nucleus (parietal heterochromatin). Complete condensation of chromosomes occurs before cell division. If chromatin is loosely packed, it is called eu- or interchromatin... This type of chromatin is much less dense when viewed under a microscope and is usually characterized by the presence of transcriptional activity. The packing density of chromatin is largely determined by histone modifications - acetylation and phosphorylation.

It is believed that so-called functional chromatin domains exist in the nucleus (the DNA of one domain contains approximately 30 thousand base pairs), that is, each chromosome region has its own “territory”. Unfortunately, the issue of the spatial distribution of chromatin in the nucleus has not been sufficiently studied yet. It is known that telomeric (terminal) and centromeric (responsible for the binding of sister chromatids in mitosis) sections of chromosomes are attached to the proteins of the nuclear lamina.

2. Chromatin

Chromatin is numerous granules stained with basic dyes, from which chromosomes are formed. Chromosomes are formed by a complex of nucleoproteins containing nucleic acids and proteins. There are two types of chromatin in the nuclei of human cells in the interphase - dispersed, weakly colored chromatin (euchromatin), formed by long, thin, intertwined fibers, metabolically very active and condensed chromatin (heterochromatin), corresponding to regions of chromosomes that are not involved in the control of metabolic activity ... Mature cells (for example, blood) are characterized by nuclei rich in dense, condensed chromatin, lying in lumps. In the nuclei of somatic cells of women, it is represented by a lump of chromatin, close to the membrane of the nucleus: this is the female sex chromatin (or Barr's little body), which is a condensed X chromosome. Male sex chromatin is represented in the nuclei of male somatic cells by a lump that glows when stained with fluorochromes. Sex chromatin determination is used, for example, to determine the sex of a child using cells obtained from the amniotic fluid of a pregnant woman.

Biochemical research in genetics is an important way of studying its basic elements - chromosomes and genes. In this article we will look at what chromatin is, find out its structure and function in the cell.

Heredity is the main property of living matter

The main processes that characterize organisms living on Earth include respiration, nutrition, growth, excretion and reproduction. The latter function is the most important for the preservation of life on our planet. How not to remember that the first commandment given by God to Adam and Eve was the following: "Be fruitful and multiply." At the cell level, the generative function is performed by nucleic acids (the constituent substance of chromosomes). These structures will be considered by us later.

Let us also add that the preservation and transmission of hereditary information to descendants is carried out according to a single mechanism that does not depend at all on the level of organization of an individual, that is, for a virus, for bacteria, and for humans, it is universal.

What is the substance of heredity

In this work, we study chromatin, the structure and functions of which directly depend on the organization of nucleic acid molecules. In 1869, the Swiss scientist Mischer discovered compounds exhibiting the properties of acids in the nuclei of cells of the immune system, which he called first nuclein, and then nucleic acids. From the point of view of chemistry, these are high molecular weight compounds - polymers. Their monomers are nucleotides with the following structure: purine or pyrimidine base, pentose and residue. Scientists have established that two species and RNA can be present in cells. They enter into a complex with proteins and form the substance of the chromosomes. Like proteins, nucleic acids have several levels of spatial organization.

In 1953, the structure of DNA was deciphered by Nobel laureates Watson and Crick. It is a molecule consisting of two chains interconnected by hydrogen bonds that arise between nitrogenous bases according to the principle of complementarity (opposite to adenine is thymine base, opposite to cytosine - guanine). Chromatin, the structure and function of which we are studying, contains molecules of deoxyribonucleic and ribonucleic acids of various configurations. We will dwell on this issue in more detail in the section “Levels of chromatin organization”.

Localization of the substance of heredity in the cell

DNA is present in such cytostructures as the nucleus, as well as in organelles capable of division - mitochondria and chloroplasts. This is due to the fact that these organelles perform the most important functions in the cell: as well as the synthesis of glucose and the formation of oxygen in plant cells. At the synthetic stage of the life cycle, the parent organelles double. Thus, as a result of mitosis (division of somatic cells) or meiosis (formation of eggs and sperm), daughter cells receive the necessary arsenal of cellular structures that provide cells with nutrients and energy.

Ribonucleic acid consists of a single strand and has a lower molecular weight than DNA. It is contained both in the nucleus and in the hyaloplasm, and is also part of many cellular organelles: ribosomes, mitochondria, endoplasmic reticulum, plastids. Chromatin in these organelles is associated with histone proteins and is part of plasmids - circular closed DNA molecules.

Chromatin and its structure

So, we have established that nucleic acids are contained in the substance of chromosomes - the structural units of heredity. Their chromatin under an electron microscope looks like granules or threadlike formations. It contains, in addition to DNA, also RNA molecules, as well as proteins that exhibit basic properties and are called histones. All of the above are nucleosomes. They are found in the chromosomes of the nucleus and are called fibrils (solenoid filaments). Summarizing all of the above, let's define what chromatin is. It is a complex compound and special proteins - histones. Double-stranded DNA molecules are wound on them, like on coils, to form nucleosomes.

Chromatin organization levels

The substance of heredity has a different structure, which depends on many factors. For example, on what stage of the life cycle the cell is going through: the period of division (meiosis or meiosis), the presynthetic or synthetic period of the interphase. From the form of a solenoid, or fibril, as the simplest form, further chromatin compaction occurs. Heterochromatin is a denser state; it is formed in intron regions of the chromosome where transcription is impossible. During the resting period of the cell - interphase, when there is no division process, heterochromatin is located in the karyoplasm of the nucleus along the periphery, near its membrane. Compaction of nuclear contents occurs in the post-synthetic stage of the cell's life cycle, that is, immediately before division.

What does the condensation of the substance of heredity depend on?

Continuing to study the question of "what is chromatin", scientists have found that its compaction depends on the histone proteins, which, along with DNA and RNA molecules, are part of the nucleosomes. They are composed of four types of proteins, called core and linker proteins. At the time of transcription (reading information from genes using RNA), the heredity substance is weakly condensed and is called euchromatin.

Currently, the features of the distribution of DNA molecules associated with histone proteins continue to be studied. For example, scientists have found that the chromatin of different loci of the same chromosome differs in the level of condensation. For example, in the places of attachment to the chromosome of the filaments of the division spindle, called centromeres, it is denser than in telomeric regions - terminal loci.

Regulatory genes and chromatin composition

The concept of the regulation of gene activity, created by the French geneticists Jacob and Monod, gives an idea of the existence of deoxyribonucleic acid regions in which there is no information about the structures of proteins. They perform purely bureaucratic - managerial functions. Called regulator genes, these parts of chromosomes, as a rule, are devoid of histone proteins in their structure. Chromatin, the determination of which was carried out by sequencing, was called open.

In the course of further research, it was found that these loci contain nucleotide sequences that prevent the attachment of protein particles to DNA molecules. Such sites contain regulatory genes: promoters, enhancers, activators. Compaction of chromatin in them is high, and the length of these regions is on average about 300 nm. There is a definition of open chromatin in isolated nuclei, in which the enzyme DNase is used. It very quickly cleaves chromosome loci lacking histone proteins. Chromatin in these areas has been called hypersensitive.

The role of the substance of heredity

Complexes, including DNA, RNA and protein, called chromatin, are involved in the ontogenesis of cells and change their composition depending on the type of tissue, as well as on the stage of development of the organism as a whole. For example, in the epithelial cells of the skin, genes such as the enhancer and the promoter are blocked by repressor proteins, and the same regulatory genes in the secretory cells of the intestinal epithelium are active and are located in the zone of open chromatin. Genetic scientists have found that DNA, which does not code for proteins, accounts for more than 95% of the entire human genome. This means that there are many more control genes than those responsible for the synthesis of peptides. The introduction of methods such as DNA chips and sequencing made it possible to find out what chromatin is, and, as a result, to carry out mapping of the human genome.

Chromatin research is very important in branches of science such as human genetics and medical genetics. This is due to the sharply increased level of occurrence of hereditary diseases, both genetic and chromosomal. Early detection of these syndromes increases the percentage of positive prognosis in their treatment.

Karyoplasm

Karyoplasm (nuclear juice, nucleoplasm) is the main internal environment of the nucleus; it occupies the entire space between the nucleolus, chromatin, membranes, all kinds of inclusions and other structures. Karyoplasm under an electron microscope looks like a homogeneous or fine-grained mass with a low electron density. It contains ribosomes, microbodies, globulins and various metabolic products in a suspended state.

The viscosity of nuclear sap is about the same as the viscosity of the basic substance of the cytoplasm. The acidity of the nuclear sap, determined by microinjection of indicators into the nucleus, turned out to be slightly higher than that of the cytoplasm.

In addition, nuclear juice contains enzymes involved in the synthesis of nucleic acids in the nucleus and ribosome. Nuclear sap is not stained with basic dyes, therefore it is called achromatin substance, or karyolymph, in contrast to areas that can stain - chromatin.

Chromatin

The main component of the nuclei - chromatin, is a structure that performs the genetic function of a cell; practically all genetic information is embedded in chromatin DNA.

Eukaryotic chromosomes look like sharply outlined structures only immediately before and during mitosis - the process of nuclear division in somatic cells. In resting, non-dividing eukaryotic cells, chromosomal material, called chromatin, looks indistinct and appears to be randomly distributed throughout the nucleus. However, when the cell prepares to divide, the chromatin thickens and gathers into its characteristic number of clearly distinguishable chromosomes.

Chromatin was isolated from the nuclei and analyzed. It is composed of very fine fibers. The main components of chromatin are DNA and proteins, among which the bulk are histones and non-histone proteins. On average, about 40% of chromatin is DNA and about 60% is proteins, among which specific nuclear proteins-histones make up from 40 to 80% of all proteins that make up the isolated chromatin. In addition, the chromatin fractions include membrane components, RNA, carbohydrates, lipids, glycoproteins.

Chromatin fibers in the chromosome are folded and form many knots and loops. DNA in chromatin is very tightly bound to proteins called histones, whose function is to pack and arrange DNA into structural units - nucleosomes. Chromatin also contains a number of non-histone proteins. Unlike eukaryotic chromosomes, bacterial chromosomes do not contain histones; they contain only a small amount of proteins that contribute to the formation of loops and condensation (compaction) of DNA.

When observing many living cells, especially plant cells, or cells after fixation and staining inside the nucleus, zones of dense matter are revealed, which are well stained with various dyes, especially basic ones. The ability of chromatin to perceive basic (alkaline) dyes indicates its acidic properties, which are determined by the fact that chromatin contains DNA in a complex with proteins. Chromosomes have the same staining properties and DNA content, which can be observed during mitotic cell division.

Unlike prokaryotic cells, DNA-containing eukaryotic chromatin material can exist in two alternative states: decondensed in the interphase and maximally compacted during mitosis, as part of mitotic chromosomes.

In non-dividing (interphase) cells, chromatin can evenly fill the volume of the nucleus or be located in separate clots (chromocenters). Often, it is especially clearly found on the periphery of the nucleus (parietal, marginal, near-membrane chromatin) or forms interweaving of rather thick (about 0.3 μm) and long cords in the form of an intranuclear network inside the nucleus.

Chromatin of interphase nuclei is DNA-carrying bodies (chromosomes), which at this time lose their compact form, loosen, decondensate. The degree of such decondensation of chromosomes can be different in the nuclei of different cells. When a chromosome or part of it is completely decondensed, these zones are called diffuse chromatin. With incomplete loosening of chromosomes in the interphase nucleus, areas of condensed chromatin (sometimes called heterochromatin) are visible. Numerous works have shown that the degree of decondensation of chromosomal material, chromatin, in the interphase can reflect the functional load of this structure. The more diffuse the chromatin of the interphase nucleus, the higher the synthetic processes in it. During the synthesis of RNA, the structure of chromatin changes. A decrease in the synthesis of DNA and RNA in cells is usually accompanied by an increase in the zones of condensed chromatin.

Chromatin is maximally condensed during mitotic cell division, when it is found in the form of bodies - chromosomes. During this period, the chromosomes do not carry any synthetic loads, they do not include the precursors of DNA and RNA.

Based on this, it can be assumed that the chromosomes of cells can be in two structural and functional states: in working, partially or completely decondensed, when they participate in the interphase nucleus, the processes of transcription and reduplication occur, and in an inactive state, in a state of metabolic rest at maximum their condensation when they perform the function of distributing and transferring genetic material to daughter cells.

Euchromatin and heterochromatin

The degree of structurization, condensation of chromatin in interphase nuclei can be expressed in different degrees. So, in intensively dividing and in little specialized cells, the nuclei have a diffuse structure, in them, in addition to the narrow peripheral rim of condensed chromatin, there are a small number of small chromocenters, while the main part of the nucleus is occupied by diffuse, decondensed chromatin. At the same time, in highly specialized cells or in cells ending their life cycle, chromatin is presented in the form of a massive peripheral layer and large chromocenters, blocks of condensed chromatin. The greater the fraction of condensed chromatin in the nucleus, the lower the metabolic activity of the nucleus. With natural or experimental inactivation of nuclei, progressive condensation of chromatin occurs and, conversely, with activation of nuclei, the proportion of diffuse chromatin increases.

However, during metabolic activation, not all areas of condensed chromatin can transform into a diffuse form. Back in the early 1930s, E. Geitz noticed that in the interphase nuclei there are constant areas of condensed chromatin, the presence of which does not depend on the degree of tissue differentiation or on the functional activity of cells. Such areas are called heterochromatin, in contrast to the rest of the chromatin mass - euchromatin (chromatin itself). According to these concepts, heterochromatin are compact sections of chromosomes, which in prophase appear earlier than other parts in the composition of mitotic chromosomes and do not decondense in telophase, passing into the interphase nucleus in the form of intensely colored dense structures (chromocenters). The centromeric and telomeric regions of chromosomes are most often constantly condensed zones. In addition to them, some areas that are part of the arms of chromosomes can be constantly condensed - intercalary, or intercalary, heterochromatin, which is also presented in the nuclei in the form of chromocenters. Such constantly condensed regions of chromosomes in interphase nuclei are now commonly called constitutive (permanent) heterochromatin. It should be noted that the regions of constitutive heterochromatin have a number of features that distinguish it from the rest of chromatin. Constitutive heterochromatin is genetically inactive; it is not transcribed, it replicates later than the rest of chromatin, it includes a special (satellite) DNA enriched with highly repetitive nucleotide sequences, it is localized in centromeric, telomeric and intercalary zones of mitotic chromosomes. The proportion of constitutive chromatin may differ from object to object. The functional significance of constitutive heterochromatin is not fully understood. It is assumed that it has a number of important functions associated with the mating of homologues in meiosis, with the structuring of the interphase nucleus, with some regulatory functions.

The rest, the bulk of the nuclear chromatin, can change the degree of its compaction depending on the functional activity; it belongs to euchromatin. Euchromatic inactive areas that are in a condensed state have come to be called facultative heterochromatin, emphasizing the optional nature of such a state.

In differentiated cells, only about 10% of genes are in an active state, the rest of the genes are inactivated and are part of condensed chromatin (facultative heterochromatin). This circumstance explains why most of the nuclear chromatin is structured.

Chromatin DNA

In a chromatin preparation, DNA usually accounts for 30-40%. This DNA is a double-stranded helical molecule similar to pure isolated DNA in aqueous solutions. Chromatin DNA has a molecular weight of 7-9106. In the composition of chromosomes, the length of individual linear (as opposed to prokaryotic chromosomes) DNA molecules can reach hundreds of micrometers and even several centimeters. The total amount of DNA entering the nuclear structures of cells, the genome of organisms, fluctuates.

DNA of eukaryotic cells is heterogeneous in composition, contains several classes of nucleotide sequences: frequently repeated sequences (> 106 times) included in the satellite DNA fraction and not transcribed; fraction of moderately repetitive sequences (102-105) representing blocks of true genes, as well as short sequences scattered throughout the genome; fraction of unique sequences carrying information for most of the proteins in the cell. All of these classes of nucleotides are linked into a single giant covalent DNA strand.

The main proteins of chromatin - histones

In the cell nucleus, the leading role in organizing the arrangement of DNA, in its compaction and regulation of functional loads belongs to nuclear proteins. Proteins in chromatin are very diverse, but they can be divided into two groups: histones and non-histone proteins. Histones account for up to 80% of all chromatin proteins. Their interaction with DNA occurs through salt or ionic bonds and is nonspecific with respect to the composition or sequences of nucleotides in the DNA molecule. A eukaryotic cell contains only 5-7 types of histone molecules. Unlike histones, the so-called non-histone proteins for the most part specifically interact with certain sequences of DNA molecules, the variety of types of proteins included in this group is very large (several hundred), and the variety of functions they perform is great.

Histones - proteins that are characteristic only of chromatin - have a number of special qualities. These are basic or alkaline proteins, the properties of which are determined by the relatively high content of such essential amino acids as lysine and arginine. It is the positive charges on the amino groups of lysine and arginine that determine the salt or electrostatic bond of these proteins with negative charges on the phosphate groups of DNA.

Histones are proteins of relatively small molecular weight. The histone classes differ from each other in the content of different essential amino acids. For histones of all classes, the cluster distribution of the main amino acids - lysine and arginine, at the N- and C-ends of the molecules is characteristic. The middle regions of histone molecules form several (3-4) b-helical regions, which are compacted into a globular structure under isotonic conditions. The non-helical ends of the protein molecules of histones, rich in positive charges, carry out their connection with each other and with DNA.

During the life of cells, post-translational changes (modifications) of histones can occur: acetylation and methylation of some lysine residues, which leads to the loss of the number of positive charges, and phosphorylation of serine residues, leading to the appearance of a negative charge. Acetylation and phosphorylation of histones can be reversible. These modifications significantly change the properties of histones, their ability to bind to DNA.

Histones are synthesized in the cytoplasm, transported to the nucleus, and bind to DNA during its replication in the S-period, i.e. syntheses of histones and DNA are synchronized. When the cell stops synthesizing DNA, histone messenger RNAs disintegrate in a few minutes and the synthesis of histones stops. The histones incorporated into chromatin are very stable and have a low rate of replacement.

Functions of histone proteins

1. The quantitative and qualitative state of histones affects the degree of compactness and activity of chromatin.

2. Structural - compacting - the role of histones in the organization of chromatin.

In order to lay huge centimeter DNA molecules along the length of the chromosome, which has a size of only a few micrometers, the DNA molecule must be twisted, compacted with a packing density equal to 1: 10,000. In the process of DNA compaction, there are several levels of packing, the first of which are directly determined by the interaction histones with DNA

Almost all of a cell's DNA is contained in the nucleus. DNA is a long linear polymer containing many millions of nucleotides. The four types of DNA nucleotides differ nitrogenous bases. Nucleotides are arranged in a sequence that is a code form for recording hereditary information.
To implement this information, it is rewritten, or transcribed into shorter m-RNA chains. The symbols of the genetic code in i-RNA are triplets of nucleotides - codons... Each codon represents one of the amino acids. Each DNA molecule corresponds to a separate chromosome, and all the genetic information stored in the chromosomes of an organism is called genome.
The genome of higher organisms contains an excess amount of DNA, this is not associated with the complexity of the organism. It is known that the human genome contains 700 times more DNA than the E. coli bacteria. At the same time, the genome of some amphibians and plants is 30 times larger than the human genome. In vertebrates, more than 90% of the DNA is irrelevant. The information stored in DNA is organized, read, and replicated by a variety of proteins.
The main structural proteins of the nucleus are proteins-histones characteristic only for eukaryotic cells. Histones- small strongly basic proteins. This property is due to the fact that they are enriched with the basic amino acids - lysine and arginine. Histones are also characterized by the absence of tryptophan. They are among the most conservative of all known proteins, for example, H4 in cow and pea is distinguished by only two amino acid residues. The complex of proteins with DNA in the cell nuclei of eukaryotes is referred to as chromatin.
When observing cells using a light microscope, chromatin is detected in the nuclei as zones of dense matter, well stained with basic dyes. An in-depth study of the structure of chromatin began in 1974, when the spouses Ada and Donald Olins described its basic structural unit, it was named the nucleosome.
Nucleosomes allow a long chain of DNA molecules to be folded more compactly. So, in each human chromosome, the length of a DNA strand is thousands of times the size of the nucleus. In electronic photographs, the nucleosome looks like a discoid particle with a diameter of about 11 nm. Its core is a complex of eight histone molecules, in which four histones H2A, H2B, H3 and H4 are represented by two molecules each. These histones form the inner part of the nucleosome - the histone core. A DNA molecule containing 146 base pairs is wound onto the histone core. It forms two incomplete turns around the histone core of the nucleosome; there are 83 nucleotide pairs per turn. Each nucleosome is separated from the next by a linker DNA sequence, which can be up to 80 nucleotides in length. This structure resembles a string of beads.
The calculation shows that human DNA having 6x10 9 nucleotide pairs should contain 3x10 7 nucleosomes. In living cells, chromatin rarely has this appearance. Nucleosomes are linked together into even more compact structures. Most of the chromatin is in the form of fibrils 30 nm in diameter. This packaging is carried out using another histone H1. There is one H1 molecule per nucleosome, which pulls together the linker site at the points where DNA enters and leaves the histone core.
DNA packaging significantly reduces its length. Nevertheless, the average length of the chromatin filament of one chromosome at this stage should exceed the size of the nucleus by a factor of 100.
The higher order chromatin structure is a series of loops, each of which contains about 20 to 100 thousand base pairs. At the base of the loop is a site-specific DNA-binding protein. Such proteins recognize certain nucleotide sequences (sites) of two spaced regions of the chromatin strand and bring them closer together.

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The nucleus is the central element of the cell. Its surgical removal discoordinates the functions of the cytoplasm. The nucleus plays a major role in the transmission of hereditary traits and protein synthesis. The transfer of genetic information from one cell to another is provided by deoxyribonucleic acid (DNA) contained in chromosomes. DNA duplication precedes cell division. The mass of the nucleus in the cells of different tissues is different and is, for example, 10-18% of the mass of the hepatocyte, 60% - in the lymphoid cells. In the interphase (intermitotic period), the nucleus is represented by four elements: chromatin, nucleola (nucleolus), nucleoplasm and nuclear membrane.

Chromatin

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Mature cells (for example, blood) are characterized by nuclei rich in dense, condensed chromatin, lying in lumps. In the nuclei of somatic cells of women, it is represented by a lump of chromatin, close to the membrane of the nucleus: this is the female sex chromatin (or Barr's little body), which is a condensed X chromosome. Male sex chromatin is represented in the nuclei of male somatic cells by a lump that glows when stained with fluorochromes. Sex chromatin determination is used, for example, to determine the sex of a child using cells obtained from the amniotic fluid of a pregnant woman.

Nucleolus

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The nucleolus is a spherical intranuclear structure that does not have a membrane. It is developed in all cells characterized by a high activity of protein synthesis, which is associated with the formation of cytoplasmic subunits, rRNA, in it. For example, nucleoli are found in the nuclei of cells capable of dividing - lymphoblasts, myeloblasts, etc.

Core membrane

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The membrane of the nucleus is represented by two sheets, the gap between which is connected to the cavity of the endoplasmic reticulum. The membrane has holes (nuclear pores) up to about 100 nm in diameter, through which macromolecules (ribonucleases, RNA) freely pass. At the same time, the nuclear membrane and pores support the microenvironment of the nucleus, ensuring the selective exchange of various substances between the nucleus and the cytoplasm. In a poorly differentiated cell, pores occupy up to 10% of the surface of the nucleus, but as the cell matures, their total surface decreases.

Nucleoplasm (nuclear juice)

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Nucleoplasm (nuclear juice) is a colloidal solution containing proteins, which ensures the exchange of metabolites and the rapid movement of RNA molecules to nuclear pores. The amount of nucleoplasm decreases with maturation or aging of the cell.

Cell division. Mitosis.

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Mitosis(Fig. 1.5) occupies only a part of the cell cycle. In mammalian cells, the mitotic phase (M) lasts about an hour.

This is followed by a postmitotic pause (G1), which is characterized by a high activity of protein biosynthesis in the cell, the processes of transcription and translation are realized. The duration of the pause is about 10 hours, but this time varies greatly and depends on the influence of regulatory factors that stimulate and inhibit cell division, on the supply of nutrients to them.

The next phase of the cell cycle is characterized by DNA synthesis (replication) (phase S) and takes about 9 hours. This is followed by the premitotic G2 phase, which lasts about 4 hours. Thus, the entire cell cycle lasts about 24 hours:

Cells can also be in the resting phase - Go, remaining outside the cell cycle for a long time. For example, in humans, up to 90% of hematopoietic stem cells are in the Go phase, but their transition from Go to G1 accelerates with an increase in the demand for blood cells.

The high sensitivity of cells to the factors regulating their division in the G1 phase is explained by the synthesis on the cell membranes during this period of hormone receptors, stimulating and inhibiting factors. For example, the division of erythroid cells in the bone marrow in the G phase stimulates the hormone erythropoietin. This process is inhibited by an erythropoiesis inhibitor - a substance that reduces the production of erythrocytes in the event of a decrease in tissue oxygen demand (Chapter 6).

The transfer of information to the nucleus about the interaction of membrane receptors with a cell division stimulator includes DNA synthesis, those. phase S... As a result, the amount of DNA in the cell changes from diploid, 2N, to tetraploid, 4N. In the G2 phase, the structures necessary for mitosis are synthesized, in particular, the proteins of the mitotic spindle.

In phase M there is a distribution of identical genetic material between the two daughter cells. The M phase itself is divided into four periods: prophase, metaphase, anaphase and telophase (Fig. 1.5.).

Prophase characterized by the condensation of DNA chromosomes forming two chromatids, each of which is one of two identical DNA molecules. Nucleola and nuclear envelope disappear. Centrioles, represented by thin microtubules, diverge to two poles of the cell, forming a mitotic spindle.

Into metaphase chromosomes are located in the center of the cell, forming a metaphase plate.In this phase, the morphology of each chromosome is most distinct, which is used in practice to study the chromosome set of a cell.

Anaphase characterized by the movement of chromatids, "pulled apart" by the fibers of the mitotic spindle to the opposite poles of the cell.

Telophase characterized by the formation of a nuclear membrane around a daughter set of chromosomes. Knowledge of the characteristics of the cell cycle is used in practice, for example, in the creation of cytostatic substances for the treatment of leukemia. Thus, the property of vincristine to be a poison for the mitotic spindle is used to stop the mitosis of leukemic cells.

Cell differentiation

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Differentiation of cells is the acquisition of specialized functions by a cell associated with the appearance in it of structures that ensure the performance of these functions (for example, the synthesis and accumulation of hemoglobin in erythrocytes characterizes their differentiation into erythrocytes). Differentiation is associated with genetically programmed inhibition (repression) of the functions of some parts of the genome and activation of others.