Methods of division of somatic and germ cells. Centromeres Segregation of chromosomes during meiosis

All chromosomes have two shoulders and the thinned area located between them - centromere, or primary constriction. In the region of the primary constriction is located kinetochore- a flat structure, the proteins of which, interacting with microtubules of the division spindle, ensure the movement of chromosomes during cell division.

The structure of the metaphase chromosome:5 - centromere; 6 - secondary constriction; 7 - satellite; 8 - chromatids; 9 - telomeres.

1 - metacentric; 2 - submetacentric; 3, 4 - acrocentric.

Metaphase chromosome consists of two chromatids. Every chromosome has primary constriction (centromere)(5), which divides the chromosome into arms.

Centromere (primary stretch) - a section of a chromosome characterized by a specific nucleotide sequence and structure. The centromere is involved in the joining of sister chromatids, the formation of the kinetochore, the conjugation of homologous chromosomes, and is involved in the control of gene expression.

It is in the region of the centromere that sister chromatids are connected in the prophase and metaphase of mitosis and homologous chromosomes in the prophase and metaphase of the first division of meiosis. On the centromeres, the formation of kinetochores occurs: proteins that bind to the centromere form an attachment point for microtubules of the fission spindle in the anaphase and telophase of mitosis and meiosis.

Deviations from the normal functioning of the centromere lead to problems in the mutual arrangement of chromosomes in the dividing nucleus, and as a result, to disturbances in the process of chromosome segregation (their distribution between daughter cells). These disorders lead to aneuploidy, which can have severe consequences (for example, Down syndrome in humans, associated with aneuploidy (trisomy) on the 21st chromosome).

When talking about the morphology of chromosomes, the following features are taken into account: the position of the centromere, the length of the arms, the presence of a secondary constriction and a satellite.

Depending on the position of the centromere in the human karyotype, chromosomes are distinguished three types :

1. Metacentric, equal-arm chromosomes: the primary constriction (centromere) is located in the center (in the middle) of the chromosome, the chromosome arms are the same.

2. Submetacentric, almost equal-arm chromosomes: the centromere is located not far from the middle of the chromosome, the arms of the chromosome differ slightly in length.

3. Acrocentric, very unequal chromosomes: the centromere is very far from the center (middle) of the chromosome, the chromosome arms differ significantly in length.

The short arm is denoted by the letter -

The long arm is denoted by the letter -

Some chromosomes have secondary constriction(6) and satellite( satellite) (7).

Secondary constriction- segment of the chromosome connecting the satellite with the body of the chromosome. In the region of the secondary constriction, ribosomal RNA genes are located, rRNA synthesis occurs, and the nucleolus is formed and assembled. Such a secondary constriction is therefore also called a nucleolar organizer. Secondary constrictions can be on the long arm of some chromosomes, and on the short arm in others.

The secondary constriction differs from the primary by the absence of a noticeable angle between the segments of the chromosome.

In humans, chromosomes have a secondary constriction 9, 13, 14, 15, 21 and 22.

Satellite ( satellite) - this is a chromosomal segment, most often heterochromatic, located distally from the secondary constriction. According to classical definitions, a satellite is a spherical body with a diameter equal to or less than the diameter of a chromosome, which is connected to the chromosome by a thin thread. There are the following 5 types of satellites:

microsatellites- spheroidal shape, small satellites with a diameter of half or even less than the diameter of the chromosome;

macrosatellites– rather large forms of satellites with a diameter exceeding half the diameter of the chromosome;

linear- satellites having the form of a long chromosome segment. The secondary constriction is considerably removed from the terminal end;

terminal- satellites located at the end of the chromosome;

intercalary are satellites located between two secondary constrictions.

Chromosomes that have a companion are called satellite, they are commonly referred to SAT chromosomes. The shape, size of the satellite and the thread connecting it are constant for each chromosome.

The satellite together with the secondary constriction make up satellite area.

The ends of chromosomes are called telomeres (9).

Telomeres(from other Greek τέλος - end and μέρος - part) - terminal sections of chromosomes. Telomeric regions of chromosomes are characterized by a lack of ability to connect with other chromosomes or their fragments and perform a protective function.

The term "telomere" was proposed by G. Möller in 1932.

In humans, the DNA of the telomeric region is a repeatedly repeated nucleotide sequence 5 "TTAGGG 3" in one of the DNA nucleotide chains.

Functions of chromosomes:

1) storage of hereditary information,

2) implementation of hereditary information,

3) the transfer of genetic material from the mother cell to the daughter.

Chromosome Rules

1. The constancy of the number. The somatic cells of the body of each species have a strictly defined number of chromosomes (in humans -46, in cats - 38, in fruit flies - 8, in dogs -78, in chickens -78).

2. Pairing. Each chromosome in somatic cells with a diploid set has the same homologous (same) chromosome, identical in size, shape, but unequal in origin: one from the father, the other from the mother.

3. Individuality. Each pair of chromosomes differs from the other pair in size, shape, alternation of light and dark stripes.

4. Continuity. Before cell division, the DNA is doubled and the result is 2 sister chromatids. After division, one chromatid enters the daughter cells and, thus, the chromosomes are continuous - a chromosome is formed from the chromosome.

They are double-stranded, replicated chromosomes that form during division. The main function of the centromere is to serve as an attachment site for the fission spindle fibers. The spindle lengthens the cells and separates the chromosomes to ensure that each new one receives the correct number of chromosomes when completed or .

The DNA in the centromeric region of a chromosome is made up of a densely packed cell known as heterochromatin, which is highly compacted and therefore not transcribed. Due to the presence of heterochromatin, the centromere region is stained with dyes darker than other parts of the chromosome.

Location

The centromere is not always located in the central region of the chromosome (see photo above). The chromosome consists of a short arm (p) and a long arm (q), which join at the centromeric region. Centromeres can be located both near the middle and in several positions along the chromosome. Metacentric centromeres are located near the center of chromosomes. Submetacentric centromeres are displaced to one side from the center, so that one arm is longer than the other. Acrocentric centromeres are located near the end of the chromosome, and telocentric centromeres are located at the end or in the telomere region of the chromosome.

The position of the centromere is easily detected in the human karyotype. Chromosome 1 is an example of a metacentric centromere, chromosome 5 is an example of a submetacentric centromere, and chromosome 13 is an example of an acrocentric centromere.

Chromosome segregation in mitosis

Before mitosis begins, the cell enters a stage known as interphase, where it replicates its DNA in preparation for cell division. Sisters are formed, which are connected at their centromeres.

In the prophase of mitosis, specialized regions on the centromeres called kinetochores attach chromosomes to spindle fibers. Kinetochores are composed of a series of protein complexes that generate kinetochore fibers that attach to the spindle. These fibers help manipulate and separate chromosomes during cell division.

At the metaphase stage, the chromosomes are held on the metaphase plate by equal forces of the polar fibers, pressing on the centromeres.

During anaphase, the paired centromeres in each individual chromosome begin to diverge from each other, as they are first centered relative to opposite poles of the cell.

During telophase, the newly formed chromosomes include separate daughter chromosomes. After cytokinesis, two different ones are formed.

Chromosome segregation in meiosis

In meiosis, the cell goes through two stages of the division process (meiosis I and meiosis II). During metaphase I, the centromeres of homologous chromosomes are oriented to opposite poles of the cells. This means that homologous chromosomes will attach in their centromeric regions to spindle fibers extending from only one of the two poles of the cell.

When the spindle fibers contract during anaphase I, the homologous chromosomes are pulled towards opposite cell poles, but the sister chromatids stay together. In meiosis II, spindle fibers extending from both cell poles attach to sister chromatids at their centromeres. Sister chromatids separate in anaphase II when the spindle fibers pull them towards opposite poles. Meiosis results in the division and distribution of chromosomes among four new daughter cells. Each cell containing only half the number of chromosomes from the original cell.

The eukaryotic chromosome is held onto the mitotic spindle by the attachment of microtubules to the kinetochore, which is formed in the centromere region.

Typically, centromeres contain chromatin enriched in satellite DNA sequences.

At mitosis sister chromatids migrate to opposite poles of the cell. This movement occurs because the chromosomes are attached to microtubules, the opposite ends of which are connected to the poles. (Microtubules are intracellular cylindrical structures that organize during mitosis to connect chromosomes to the poles of the cell.)

Sites in two regions, where the ends of microtubules are organized - near the centriole at the poles and on the chromosomes - are called MTCs (centers of microtubule organization).

Picture below schematically illustrates the process of separation of sister chromatids that occurs between the metaphase and telophase of mitosis. The region of the chromosome responsible for its segregation during mitosis and meiosis is called the centromere. Through microtubules, the centromere of each sister chromatid is drawn to opposite poles and pulls the chromosome associated with it. The chromosome provides a mechanism for attaching a large number of genes to the division apparatus.

It contains website, which holds the sister chromatids together until the segregation of individual chromosomes. It looks like a constriction to which all four arms of the chromosome are attached, as shown in the figure below, which shows sister chromatids in metaphase.

Centromere required for chromosome segregation. This is confirmed by the properties of chromosomes, the integrity of which has been violated. As a result of the break, one fragment of the chromosome retains the centromere, while the other, called acentric, does not contain it. The acentric fragment is unable to attach to the mitotic spindle, as a result of which it does not enter the nucleus of the daughter cell.

Areas chromosomes, flanking the centromere, usually contain , rich in satellite sequences, and a significant amount of heterochromatin. Since the entire mitotic chromosome is condensed, centromeric heterochromatin is invisible in it. However, it can be visualized using a staining technique that reveals C-bands. In the figure below, a dark-colored region is present in the region of all centromeres. This pattern is seen most often, although heterochromatin may not be found in the region of each centromere. This suggests that centromeric heterochromatin, apparently, is not a necessary component of the division mechanism.

Field of education centromeres in a chromosome is determined by the primary structure of DNA (although the specific sequence is known only for a small number of chromosomes). Centromere DNA binds certain proteins that form the structure that allows chromosomes to attach to microtubules. This structure is called the kinetochore. It is a stained fibrillar structure with a diameter or length of about 400 nm.

Kinetochore provides the creation CMTC on the chromosome. The figure below shows the hierarchical organization of centromere DNA binding to microtubules. Proteins associated with centromere DNA are associated with other proteins, which in turn are associated with microtubules.

When sister chromatid centromeres begin to move towards the poles, the chromatids remain held together by "gluing" proteins called cohesins. First, the chromatids separate at the centromere, and then, in anaphase, when the cohesins are destroyed, they completely separate from each other.

Functions

The centromere is involved in the joining of sister chromatids, the formation of the kinetochore, the conjugation of homologous chromosomes, and is involved in the control of gene expression.

It is in the region of the centromere that sister chromatids are connected in the prophase and metaphase of mitosis and homologous chromosomes in the prophase and metaphase of the first division of meiosis. On the centromeres, the formation of kinetochores occurs: proteins that bind to the centromere form an attachment point for microtubules of the fission spindle in the anaphase and telophase of mitosis and meiosis.

Deviations from the normal functioning of the centromere lead to problems in the mutual arrangement of chromosomes in the dividing nucleus, and as a result, to disturbances in the process of chromosome segregation (their distribution between daughter cells). These disorders lead to aneuploidy, which can have severe consequences (for example, Down's syndrome in humans, associated with aneuploidy (trisomy) on the 21st chromosome).

Centromeric sequence

In most eukaryotes, the centromere does not have a specific nucleotide sequence corresponding to it. It usually consists of a large number of DNA repeats (eg, satellite DNA) in which the sequence within the individual repeat elements is similar but not identical. In humans, the main repeat sequence is called the α-satellite, but there are several other types of sequences in this region. It has been established, however, that there are not enough α-satellite repeats to form a kinetochore and that functioning centromeres are known that do not contain α-satellite DNA.

Inheritance

Epigenetic inheritance plays a significant role in determining the location of the centromere in most organisms. Daughter chromosomes form centromeres in the same places as the maternal chromosome, regardless of the nature of the sequence located in the centromere region. It is assumed that there must be some primary way to determine the location of the centromere, even if its location is subsequently determined by epigenetic mechanisms.

Structure

The DNA of the centromere is usually represented by heterochromatin, which may be essential for its functioning. In this chromatin, the normal histone H3 is replaced by the centromere-specific histone CENP-A (CENP-A is characteristic of baker's yeast). S.cerevisiae, but similar specialized nucleosomes seem to be present in all eukaryotic cells). The presence of CENP-A is thought to be required for the assembly of the kinetochore at the centromere and may play a role in the epigenetic inheritance of centromere location.

In some cases, for example, in a nematode Caenorhabditis elegans, in Lepidoptera, and also in some plants, chromosomes holocentric. This means that the chromosome does not have a characteristic primary constriction- a specific site to which microtubules of the fission spindle are predominantly attached. As a result, the kinetochore is diffuse in nature, and microtubules can attach along the entire length of the chromosome.

centromere aberrations

In some cases, a person noted the formation of additional neocentromere. This is usually combined with inactivation of the old centromere, since dicentric chromosomes (chromosomes with two active centromeres) are usually destroyed during mitosis.

In some unusual cases, spontaneous formation of neocentromeres on fragments of disintegrated chromosomes has been noted. Some of these new positions were originally euchromatin and did not contain alpha satellite DNA at all.

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See what "Centromere" is in other dictionaries:

Centromere ... Spelling Dictionary

Kinetochor Dictionary of Russian synonyms. centromere noun, number of synonyms: 1 kinetochore (1) ASIS synonym dictionary. V.N. Trishin ... Synonym dictionary

- (from the center and the Greek meros part) (kinetochore) a section of the chromosome that holds together its two strands (chromatids). During division, centromeres direct the movement of chromosomes towards the poles of the cell ... Big Encyclopedic Dictionary

Centromere, part of the chromosome that appears only in the process of cell division. When chromosomes shorten during MEIOSIS or MITOSIS, centromeres appear as constrictions that do not contain any genes. With their help, chromosomes are attached to ... ... Scientific and technical encyclopedic dictionary

- (from Latin centrum, Greek kentron middle point, center and Greek meros part, share), kinetochore, a section of the chromosome that controls its movement to different poles of the cell during mitosis or meiosis; the site of attachment to the chromosome threads ... ... Biological encyclopedic dictionary

centromere- A limited area in the chromosome, including the spindle attachment site during mitosis or meiosis Biotechnology Topics EN centromere … Technical Translator's Handbook

Centromere- * centromere * centromere or kinetochore is a conservative region of the eukaryotic chromosome, to which spindle threads (see) are attached during mitosis (see). The DNA forming C. consists of three domains (elements) CDE I, CDE II and CDE III. CDE I and... Genetics. encyclopedic Dictionary

- (from the center and the Greek méros part) (kinetochore), a section of the chromosome that holds together its two strands (chromatids). During division, centromeres direct the movement of chromosomes towards the poles of the cell. * * * CENTROMETER CENTROMETER (from the center (see DIRECT BOARD) and ... encyclopedic Dictionary

Centromere centromere. A section of a monocentric chromosome in which sister chromatids are interconnected and in the region of which spindle threads are attached, ensuring the movement of chromosomes to the poles of division; usually centromeric areas ... ... Molecular biology and genetics. Dictionary.

centromere- centromera statusas T sritis augalininkystė apibrėžtis Pirminė chromosomos persmauga, prie kurios prisitvirtina achromatinės verpstės siūlai. atitikmenys: engl. centromere; kinetochore rus. kinetochore; centromere ... Žemės ūkio augalų selekcijos ir sėklininkystės terminų žodynas

No. 9, 2007

© Vershinin A.V.

Centromeres and telomeres of chromosomes

A.V. Vershinin

Alexander Vasilievich Vershinin, Doctor of Biological Sciences, Chief Scientific Associate Institute of Cytology and Genetics SB RAS.

What are chromosomes, today almost everyone knows. These nuclear organelles, in which all genes are localized, constitute the karyotype of a given species. Under a microscope, chromosomes look like uniform, elongated dark rod-shaped structures, and the picture seen is unlikely to seem like an intriguing sight. Moreover, the preparations of the chromosomes of a great many living creatures that live on Earth differ only in the number of these rods and modifications of their shape. However, there are two properties that are common to chromosomes of all species. The first is the presence of an obligatory compression (or constriction) located either in the middle or displaced to one of the ends of the chromosome, called the “centromere”. The second is the presence at each end of the chromosome of a specialized structure - telomeres (Fig. 1). Various genes located along the arms (parts of the chromosome from the centromere to the physical end) of the chromosomes, together with regulatory DNA sequences, are responsible for performing a variety of functions. This ensures the uniqueness of the genetic information encoded in each arm of each individual chromosome.

Centromeric and telomeric regions occupy a special position, because they perform extremely important, but the same functions in the chromosomes of all eukaryotic species. Numerous studies have not yet given a clear answer to the question of which molecular structures are responsible for performing these functions and how they perform them, but obvious progress in this direction has been achieved in recent years.

Prior to the elucidation of the molecular structure of centromeres and telomeres, it was believed that their functions should be determined (encoded) by universal and at the same time specific for these regions DNA sequences. However, direct determination of the primary nucleotide sequence (DNA sequencing) was complicated by the fact that these regions, as a rule, coexist in chromosomes with regions of high concentration of repetitive DNA sequences. What is known today about these functionally important regions of chromosomes?

Centromeres

By the middle of the last century, numerous cytological studies showed the decisive role of the centromere in the morphology of chromosomes. Later it was found that the centromere, together with the kinetochore (a structure consisting mainly of proteins), is responsible for the correct divergence of chromosomes into daughter cells during cell division. The guiding role of the centromere in this process is obvious: after all, it is to it that the division spindle is attached, which, together with the cell centers (poles), constitutes the apparatus of cell division. Due to the contraction of the spindle threads, the chromosomes move during division to the poles of the cell.

Five stages of cell division (mitosis) are usually described. For simplicity, we will focus on three main stages in the behavior of the chromosomes of a dividing cell (Fig. 2). At the first stage, there is a gradual linear contraction and thickening of chromosomes, then a cell division spindle is formed, consisting of microtubules. On the second, the chromosomes gradually move towards the center of the nucleus and line up along the equator, probably to facilitate the attachment of microtubules to the centromeres. In this case, the nuclear envelope disappears. At the last stage, the halves of the chromosomes - the chromatids - diverge. It seems that microtubules attached to the centromeres, like a tug, pull the chromatids to the poles of the cell. From the moment of divergence, the former sister chromatids are called daughter chromosomes. They reach the spindle poles and come together in parallel. The nuclear envelope is formed.

Rice. 2. Main stages of mitosis.
From left to right: compaction of chromosomes, formation of a fission spindle; alignment of chromosomes along the equator of the cell,
attachment of the spindle to the centromeres; movement of chromatids towards the poles of the cell.

With careful observation, it can be seen that in the process of cell division in each chromosome, the centromere is in a constant position. It maintains a close dynamic relationship with the cell center (pole). Centromere division occurs simultaneously in all chromosomes.

The sequencing methods developed in recent years have made it possible to determine the primary structure of the DNA of extended sections of human centromeres, fruit flies Drosophila and plants Arabidopsis. It turned out that in the chromosomes of both humans and plants, centromeric activity is associated with a block of tandemly organized repeats (monomers) of DNA that are close in size (170–180 nucleotide pairs, bp). Such regions are called satellite DNA. In many species, including those that are evolutionarily distant from each other, the size of monomers is almost the same: different types of monkeys - 171 bp, corn - 180 bp, rice - 168 bp, Chironomus insect - 155 bp. Perhaps this reflects the general requirements required for centromere function.

Despite the fact that the tertiary structure of human and Arabidopsis centromeres is organized in the same way, the primary nucleotide sequences (or the order of nucleotides) in their monomers turned out to be completely different (Fig. 3). This is surprising for a region of the chromosome that performs such an important and versatile function. However, when analyzing the molecular organization of the centromeres in Drosophila, a certain structural pattern was found, namely, the presence of sections of monomers of approximately the same size. Thus, in Drosophila, the X-chromosome centromere consists mainly of two types of very short simple repeats (AATAT and AAGAG), interrupted by retrotransposons (mobile DNA elements) and “islands” of more complex DNA. All these elements were found in the Drosophila genome and outside the centromeres, however, DNA sequences characteristic of each centromere were not found in them. This means that centromeric DNA sequences by themselves are not sufficient and are not necessary for the formation of a centromere.

Rice. 3. DNA structure in human and plant centromeres.

Rectangles correspond to tandem organized monomers with an identical nucleotide sequence inside (the primary structure of DNA). In different species, the primary structure of DNA monomers differs, and the secondary is a helix. The sequence of monomers reflects the higher level structural organization of DNA.

The functional role of the centromeric structure of chromatin is confirmed by the presence of histone H3 variants specific for each biological species in centromeric chromatin: in humans they are called CENP-A, in plants - CENH3. Among the many proteins present in the kinetochore, only two, CENH3 and centromeric protein C (CENP-C), bind directly to DNA. Possibly, it is CENH3, interacting with other histones (H2A, H2B, and H4), that forms and determines the type of nucleosomes specific for the centromere. Such nucleosomes can serve as a kind of anchor for the formation of the kinetochore. Histone H3 variants in the centromeres of various species are similar to the canonical H3 histone molecule in the sites of interaction with other histone proteins (H2A, H2B, H4). However, the site of the centromeric histone H3, which interacts with the DNA molecule, is apparently under the action of driving selection. As discussed, the primary structure of centromeric DNA differs between species, and it has been suggested that centromeric histone H3 co-evolves with centromeric DNA, particularly in Drosophila and Arabidopsis.

The discovery of the centromeric histone H3 gave rise to an extreme point of view, according to which the centromeric function and its complete independence from the primary structure of DNA is determined by the nucleosomal organization and this histone. But are these factors sufficient for full centromere activity? Models that ignore the role of primary DNA structure must assume a random distribution of changes in centromeric DNA structure in different populations in the absence of selection. However, analysis of satellite DNA in human centromeres and Arabidopsis revealed conserved regions as well as regions with higher than average variability, indicating selection pressure on centromeric DNA. In addition, artificial centromeres were obtained only with human a-satellite repeats amplified from natural centromeres, but not from a-satellites of the pericentromeric regions of chromosomes.

There are fewer fundamental difficulties in explaining models in which the decisive factor in determining the position of the centromere (conserved from generation to generation) and its functions is the tertiary (or even higher order) structure of DNA. Its conservatism allows for large variations in nucleotide sequence and does not preclude fine tuning of the primary structure.

In recent years, it has become obvious that there are no universal DNA sequences that directly determine the functions of centromeres and telomeres. In these regions of chromosomes, DNA serves as a platform for the assembly of complex, multicomponent DNA-protein complexes, which ensure the performance of these functions. More details about the complementary organization of these complexes and their coordinated functioning can be found in our review. Along with the components specific for centromeres and telomeres, these complexes also include those that are involved in the performance of several functions, sometimes even opposite ones. For example, the Ku70/80 heterodimer is part of telomeres and functions as a positive regulator of telomere length in yeast and a negative regulator in Arabidopsis. At the same time, this protein is involved in the recognition of chromosome breaks and their restoration. Undoubtedly, one of the most topical areas of research is the identification of the molecular nature of the mechanisms of regulation of various molecular complexes that ensure the activity of centromeres and telomeres.

The work was supported by the Russian Foundation for Basic Research (project 04-04-48813), INTAS (03-51-5908)
and the Program of Integration Projects of the SB RAS (project 45/2).

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