From Big Medical Encyclopedia

REPRODUCTION OF CHROMOSOMES (Latin re-the prefix meaning repetition, resuming + producere to make, create; chromosomes) — reproduction by a cell of all chromosomes which are contained in it at preservation of specificity of each of them. River x. occurs in any cycle of cellular division; it is necessary for providing two daughter cells with a full range of identical chromosomes (see). This process is called also reduplication or identical reduplication.

Semi-conservative is the cornerstone of a reproduction of a chromosome replication (see) main its making component — molecule DNA (see. Deoxyribonucleic acid ), i.e. each of two chains of initial molecule DNA complementary each other serves as a matrix, on a cut the polynucleotide chain (so-called konvariantny reduplication) is synthesized new, complementary by it. Thus, both affiliated molecules DNA contain both the old, and again synthesized polynucleotide chain and therefore R. x. is autoreproduktsiy (autoduplikation). Ability of a chromosome to an autoreproduktion provides genetic succession of cells and organisms among their generations.

by Fig. 1. Drug of metaphase chromosomes of the person: different coloring of sister chromatids is caused by unequal inclusion of a 5-bromdezoksiuridin; shooters specified sisterly chromatid interchanges.

Main patterns of R. x. are found out by studying of distribution of marked nucleosides in metaphase chromosomes. After inclusion of 3H-thymidine or a 5-bromdezoksiuridin in DNA throughout the S-period (the period of synthesis of DNA) all chromosomes of set in the first metaphase (see. Mitosis ) look marked evenly on length. In the absence of the marked predecessor of DNA in the S-period of the second division in its metaphase the tag is found only in one of two sister chromatids of each chromosome (fig. 1). Such distribution of a tag in the first and second divisions opened in 1957 by Taylor (J. N of Taylor), was the proof a semi-game-servativnogo of nature of replication of chromosomal DNA and allowed to formulate important regulations on submicroscopic structure of a chromosome. Distribution of a tag in the so-called diplochromosomes (which did not disperse in a mitosis in daughter cells two chromosomes each of to-rykh reduplitsirovatsya in the subsequent cellular cycle) showed that at matrix R. x. there is constant dimensional orientation of matrix subunits of a hrokhmosoma — the new subunit is always under construction outside from old.

Different marking of sister chromatids 3H-thymidine or 5-bromdezoksiuridiny in the second cycle of division after inclusion of a tag led to opening of global exchanges chromosomal material between sister chromatids in identical points on length of chromatids (so-called sisterly chromatid interchanges). Researches of sisterly chromatid interchanges especially intensively began to be conducted from 70th 20 century after as a tag began to use 5-bromdezoksiuridin, providing the accuracy and simplicity of the accounting of exchanges on differentsialno the painted sister chromatids.

Sisterly chromatid interchanges form during DNA replication; the rupture of both threads of molecule DNA in both chromatids is necessary for implementation of such exchange in a point of exchange. Molecular mechanisms and biol. value of sisterly chromatid interchanges remain in many respects not clear. They are found in all types of somatic cells as in vivo, and in cultures of cells, and also in meiotic cells in all metaphytes. The number of exchanges in different cells a miscellaneous. A certain share of exchanges in each cell is induced used for their detection by 3H-thymidine or 5-bromdezoksiuridiny, however a part of sisterly chromatid interchanges is spontaneous. In cells of the person (the cultivated lymphocytes of blood and fibroblasts of skin, a cell of marrow) the number of exchanges for a cell averages 6 — 9. Distribution of exchanges on chromosomes of set (see. Chromosomal complement ) in general uniform and generally correlates with a length of a chromosome. However in chromosomes of the E, F and G groups observe lowered, and in chromosomes of group B — the raised number of exchanges in comparison with the expected sizes calculated from an assumption of strict proportionality between number of sisterly chromatid interchanges and length of a chromosome. Within a chromosome exchanges in eukhromatino-vy areas meet more often than in heterochromatinic (see. Chromatin ), i.e. their distribution on length of a chromosome uneven.

Fig. 2. Drug of metaphase chromosomes of the person after inclusion of a 5-bromdezoksiuridin on a final piece of the S-period: the light-painted sites on length of each chromosome correspond early we reduplitsiruyushchitsya to sites.

The tag entered on any piece of the S-period and defined in metaphase of a mitosis is found in many chromosomes of set. The sequence of a reproduction of its sites is constant and specific to each chromosome. This point was finally made during the studying of the sequence of a reproduction of sites of chromosomes by means of a 5-bromdezoksiuridpn (fig. 2).

Assume that the sites of chromosomes which are reproduced in a certain piece of the S-period consist of groups it is similar the replicated regshikon (elementary units of replication). These sites by the sizes and localization correspond to those, to-rye are built of the chromatin different in the structural and functional relation, and come to light in a chromosome by means of differential coloring. Specificity of an order of DNA replication in each chromosome of set at use of a 5-bromdezoksiuridin allows to distinguish in a karyotype of the person (see. Karyotype ) all 22 couples of autosomes and sexual X-and Y-chromosomes. Two X-chromosomes in female somatic cells at the person as well as at other mammals, significantly differ among themselves on time of a reproduction. One of them which is exposed to a genetic inactivation begins much later and finishes the reproduction in comparison with other, genetically active X-chromosome.

The person has all chromosomes, except one of X-chromosomes in female cells, begin a reproduction at the same time. Late reduplitsiruyushchiyesya sites of chromosomes correspond to heterochromatinic sites, synthesis of DNA goes to them more intensively. The general duration of a reproduction of any chromosome makes several hours. The sequence of DNA replication in this chromosome same in cells of a different differentiation and at different individuals. Intercellular or interindividual distinctions are possible on those chromosomes, to-rye contain large blocks of heterochromatin and the sizes to-rykh can vary considerably. At the person it is autosomes 1,9,13 — 16,21,22 and a sexual Y-chromosome. In this case distinctions according to the drawing of DNA replication concern the corresponding varying segments and are quantitative, but not qualitative. The order of DNA replication in a chromosome significantly does not change even then when there is a deviation from diploid number (e.g., at a trisomy of a chromosome 21 or monosomies of X-chromosome) or restructuring. Stability of the drawing of replication of a chromosome is used in a wedge, cytogenetics at identification of chromosomes in case of their numerical or structural deviations. The exception is made by X-autosomal translocations (see), at to-rykh the delta time of reduplication of an autosomal segment is described that explain it with the genetic inactivation induced by certain regions of the inactivated X-chromosome.

The chromosome of metaphytes is the line structure subdivided on the length into the sites differing with features of a structure of DNA, its transkriptsionny ability, a condition of condensation in an interfazny kernel and the nature of packaging of threads of dezoksinukleoproteid in a metaphase chromosome. It is possible to add R.'s time to these characteristics x., a cut determines along with other characteristics structurally functional differentiation of a chromosome by length. Therefore studying of the sequence of a reproduction of sites of a chromosome is important for recognition of chromosomes in cases of change of their number or structure leading to multiple inborn malformations (see. Chromosomal diseases ). Definition of an order of R. x. found especially broad application in a wedge, cytogenetics at inspection of people with disturbances of sexual, intellectual and somatic development, competing in this respect with method of differential coloring of chromosomes and having forced out a method autoradiography (see). Methods of inclusion of a 5-bromdezoksiuridin and differential coloring of chromosomes provided significant progress a wedge, cytogenetics (see). They became a basis for identification of new forms of the chromosomal diseases caused by deletions or duplications of sites of chromosomes (see. Deletion , Duplication ).

R. found during the studying x. sisterly chromatid interchanges use for assessment of mutagen activity of environmental factors (see. Mutagens , Mutation ). Comparative simplicity and accuracy of the accounting of exchanges belongs to advantages of this test. The new test has no advantages before the test of aberation chromosomes during the studying of mutagen effect of ionizing radiation as it is not the expressed inductor of sisterly chromatid interchanges. However the frequency of exchanges is a sensitive efficiency factor of action on the chromosomal device of the alkylating and nek-ry other chemical substances therefore the accounting of formation of sisterly chromatid interchanges is used in a combination with other tests for assessment of mutagen activity of chemical connections. Frequency of sisterly chromatid interchanges can be used also at diagnosis of the nek-ry hereditary diseases with an autosomal and recessive mode of inheritance caused by mutations of the genes controlling the fermental systems participating in a reparation of the damaged DNA. The chromosomal instability which is expressed in increase

in frequency of aberation chromosomes is characteristic of these diseases. At Blum's syndrome (see. Poikiloderma ) frequency of sisterly chromatid interchanges in sick cells by 10 times and more exceeds the frequency of exchanges in cells of normal individuals. Thus, this sign can serve as the test at diagnosis, including and prenatal, Blum's syndrome. At nek-ry forms of a pigmental xeroderma (see. Xeroderma pigmental ), the damages of DNA caused by Uv-radiation which are characterized by disturbances of a reparation the frequency of sisterly chromatid interchanges under certain conditions is higher than UF-radiation of cells, than in cells of healthy people. Frequency of exchanges, insufficient in comparison with norm, in response to action of the alkylating bifunctional agents is described at the anemia caused by genetic defect of the DNK-ekzonukleazy enzyme participating in a reparation of damages of DNA. It is possible to assume that progress in molecular genetics will lead to opening of the hereditary diseases caused by mutations of the genes controlling the complex fermental systems providing R. x.; on a nek-eye to data, it is possible to carry Blum's syndrome to such diseases.

All methods of studying of R. x. are based on introduction to a cell during synthesis of DNA (S-period) of predecessors of DNA — nucleosides, marked by radioisotope of hydrogen — hyzone (3H). Definition of inclusion of a tag is carried out or on interfazny kernels, or on mitotic chromosomes. According to Taylor's proposal, as a radioactive label almost everywhere use the specific predecessor of DNA 3 H-thymidine. Apply a method of an autoradiography to identification of its inclusion in a chromosome. However this method in studying of a reproduction of the whole chromosomes is more and more forced out by method of inclusion of predecessors of DNA, marked the non-radioactive bromine. For this purpose use hl. obr. analog of thymidine 5-bromdezoksiuridin. Inclusion of a 5-bromdezoksiuridin in sites of chromosomes can be revealed on drugs of metaphase chromosomes on their changed colourability (see fig. 1 and 2). As dyes apply nek-ry flyuorokhroma (e.g., acridic orange) or the main dyes (iapr., Romanovsky's paint — Gimza). Use of a 5-bromdezoksiuridin instead of 3 H-thymidine considerably increased resolving power of methods of optical studying of R. x.

Bibliography: Boston To. and and e r E. Hromosoma of an eukaryotic cell, the lane with English, M., 1981; Yepifanova O. I., Tersky V. V. and Zakharov of A. F. Radioavtografiya, M., 1977; Zakharov A. F. Chromosomes of the person (problem of the linear organization), M., 1977, bibliogr.; it, Sisterly chromatid interchanges, a phenomenon and mechanisms, in book: Genetics of the person, under the editorship of N. P. Bochkov, t. 3, page 76, M., 1978, bibliogr.; Fundamentals of cytogenetics of the person, under the editorship of A. A. Prokofieva-Belgovskaya, page 104, M., 1969.

A. F. Zakharov.