Chromosome coordinated replication

In general, a given pair of chromosomes will replicate simultaneously and within a fixed portion of the S phase upon every replication. On a chromosome, clusters of replication units replicate coordinately. The na-mre of the signals that regulate DNA synthesis at these levels is unknown, but the regulation does appear to be an intrinsic property of each individual chromosome. 

Blow JJ, Tanaka TU. The chromosome cycle coordinating replication and segregation. Second in the cycles review series. EMBO Rep. 2005 6 1028-1034. 

Intercellular control of the functions of mammalian cells has been long since evidenced by observations of experimental embryologists and, in recent years, one form of it, contact inhibition, discovered by Abercrombie and Heayesman (1954), has been a most popular subject of study. Contact inhibition is certainly one type of control which is generally not found in bacteria and this difference must be directly correlated with differences between the structures of bacterial and mammalian cell surfaces. Other differences between the structures of bacterial and mammalian cells are the presence in the latter of a nuclear membrane and of an elaborate mitotic apparatus. We shall have little to say about the latter and shall consider mainly the nuclear membrane, to which, we think, are delegated certain functions assumed, in bacteria, by the cell membrane and concerned with die coordinated replication of the chromosomes (Jacob et al., 1963). This idea represents one of a number of inferences from recent observations made in our laboratories on interspecific somatic hybrids between mammalian cells, and it is the primary purpose of this paper to present the evidence on which it is based (Note 2). 

Stubblefield was able to study the incorporation of tritiated thymidine into the different karyomeres of the same cell. While each of the individual nuclei was able to synthesize DNA and to enter mitosis, the distribution of label in the interphase nuclei and in the chromosomes clearly demonstrated asynchrony of DNA synthesis in the different nuclei of a single cell. Thus, multinucleated interphase cells were found which contained label in only some of the karyomeres. Since all these karyomeres entered mitosis simultaneously, the (tetraploid) metaphases were characterized by the presence of both heavily labeled and completely unlabeled chromosomes (Note 10). This experiment shows that the coordinated replication of the chromosomes breaks down when the chromosomes are segregated into several nuclei, or, putting it the other way around, that the coordination of the cycles of individual chromosomes requires that they be located within a single nucleus. 

Further, we would like to speculate that the initiation of DNA synthesis is mediated by some reaction of the nuclear membrane, analogous to that of the cell membrane of bacteria which, according to Jacob et al. (1963), triggers the coordinated replication of then-chromosomes and episomes. 

Re combinational DNA repair of a circular bacterial chromosome, while essential, sometimes generates deleterious byproducts. The resolution of a Holliday junction at a replication fork by a nuclease such as RuvC, followed by completion of replication, can give rise to one of two products the usual two monomeric chromosomes or a contiguous dimeric chromosome (Fig. 25-41). In the latter case, the covalently linked chromosomes cannot be segregated to daughter cells at cell division and the dividing cells become stuck. A specialized site-specific recombination system in E. coli, the XerCD system, converts the dimeric chromosomes to monomeric chromosomes so that cell division can proceed. The reaction is a site-specific deletion reaction (Fig. 25-39b). This is another example of the close coordination between DNA recombination processes and other aspects of DNA metabolism. 

The rate of DNA replication is coordinated with the rate of cell division. Thus, a bacterial culture growing in a rich medium has a short generation-time and must accomplish chromosome replication... 

Notable members comprising the Family B polymerases include the prototypical E. coli Pol II, as well as eukaryotic polymerases, Pol a, Pol S, Pol e, and Pol (. In humans, the coordinated efforts of Pol a, Pol 8, and Pol e are responsible for leading and lagging strand synthesis during nuclear chromosomal replication prior to... 

Lasers and cancer So what use do scientists have for these tiny tweezers One group of scientists is using them to study cell organelles. They are studying the forces exerted by mitotic spindles— the grouping of microtubules that coordinates cell division. The spindles guide replicated chromosomes to opposite sides of the cell—a key role in cell division. However, scientists do not know exactly how the spindles perform this function. 

Of considerable importance are the structural motifs termed telomeres that have been identified at the ends of chromosomal DNA. Such motifs provide chromosomal stability and have been implicated in cell replications and a putative role in the mechanism of aging. Such structures (illustrated in Figure 6) are formed when four guanine bases form stable four-stranded helices. Such tetrads are stabilized principally by potassium ion, although sodium ion stabilization has also been characterized." " A cubic coordination motif is generated by the eight 06 atoms from the guanine bases. 

How is initiation coordinated in different replication units during S phase There are several ways that coordinated initiation can be envisaged. For example, the synthesis of initiator molecules that select specific rephcation units for duplication may occur at a select time during S phase. Alternatively, initiation sites in DNA may be protected from the initiation apparatus so that initiation in any replication unit is possible only when the initiation sites have been exposed by contact with other structures such as the cell membrane. Such models imply a means of physically changing the orientation of whole chromosomes during S so that all initiation sites are placed in contact at some stage with the nuclear membrane. 

A hypothetical model of replication of the E. coli chromosome, worked out in very great detail, has recently been published by Sibatani and Hiai (1964). Since this is purely hypothetical at the present time, I shall not analyze all its aspects in detail, although I should mention that these workers have presented other possible explanations of the precise coordination between the individual acts of replication. 

The notion that the rate of DNA synthesis and of other events of the chromosomal cycle, and, hence, the duration of this cycle (rather than the time of initiation of DNA synthesis), is diflFerent in different karyomeres, which contain different numbers and kinds of chromosomes, is not farfetched. Moreover, it has two advantages (1) It resolves the apparent conflict between the observations of Stubblefield on the asynchrony of karyomeres and those on the synchrony of (complete) nuclei in bi- and multinucleate cells (Note 12) and (2) it makes it easier to visualize the coordination of the replication of all chromosomes in hybrids between cells differing in generation times. We shall therefore conclude that a single, basic rate and timetable of chromosomal changes is established only when all the chromosomes are enclosed in a single nuclear membrane. 

Spurious coordination of this sort is postulated by Sandberg et human cell line containing many binucleate cells, of tetraploid metaphases with only one half of labeled chromosomes. These metaphases are presumed to arise from (the rare) binucleate cells of which one nucleus replicated its DNA considerably ahead of the other, and then awaited completion of DNA replication in its mate before going into metaphase (i.c., p. 105). 

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