Eukaryotic chromosome replication

FIGURE 24-5 Eukaryotic chromosomes, (a) A pair of linked and condensed sister chromatids from a human chromosome. Eukaryotic chromosomes are in this state after replication and at metaphase during mitosis, (b) A complete set of chromosomes from a leukocyte from one of the authors. There are 46 chromosomes in every normal human somatic cell. 

Artificial chromosomes. Another approach to understanding eukaryotic replication, similar to the... 

Multiple-origin model for eukaryotic chromosomal DNA replication, (a) Autoradiograph of short-term labeling of a eukaryotic chromosome during replication and its interpretation. (b) Overall replication scheme for a eukaryotic chromosome. Only a short region of the chromosome is shown. It is believed that replication origins are relatively free of proteins. 

Synthesis at the ends of a eukaryotic chromosome. One end of the linear DNA of a eukaryotic chromosome is diagrammed. A flush-ended DNA duplex presents a problem for completing synthesis at the 5 end (a). This is because of the RNA primer requirement for DNA synthesis. When the primer at the 5 end is removed there is no conventional way to fill the gap. A solution to this problem is shown in (b). The ends of eukaryotic chromosomal DNAs consist of highly repetitious tandem repeats (telomeres). These repeats on the 3 end serve as both primer and template for extending the 3 end. The extended 3 end can accommodate a primer RNA, so after chromosomal DNA replication no loss occurs from the 5 end of the DNA. Another process is needed to remove the extension from the 3 end. New synthesis is indicated in red. The zigzag represents primer. 

Multiple replicons In eukaryotes, replication of chromosomal DNA occurs only in the S phase of the cell cycle. As for bacterial DNA (see Topic F3), eukaryotic DNA is replicated semi-conservatively. Replication of each linear DNA molecule in a chromosome starts at many origins, one every 3-300 kb of DNA depending on the species and tissue, and proceeds bi-directionally from each origin. The use of multiple... 

Fig. 2. Replication of eukaryotic chromosomal DNA. Replication begins at many origins and proceeds bi-directionally at each location. Eventually the replication eyes merge together to produce two daughter DNA molecules, each of which consists of one parental DNA strand (thin line) and one newly synthesized DNA strand (thick line).

Multiple Replicon Model of Eukaryotic Chromosomal DNA Replication. 

A short segment of a eukaryotic chromosome during replication. 

In eukaryotes the DNA replication rate is 50 nucleotides per second. How long does the replication of a chromosome of 150 million base pairs take If eukaryotic chromosomes were replicated like those of prokaryotes, the replication of a... 

As discussed in Chapter 4, eukaryotic chromosomes are replicated from multiple origins. Some of these Initiate DNA replication early in the S phase, some later, and still others toward the end. However, no eukaryotic origin Initiates more than once per S phase. Moreover, the S phase continues until replication from all origins along the length of each chromosome results in replication of the chromosomal DNA In Its entirety. These two factors ensure that the correct gene copy number is maintained as cells proliferate. 

Various methods have been used to calculate the average size of replication units in different eukaryote chromosomes (Cairns, 1966 Painter et al., 1966 Haut et al., 1966 Okada, 1968). Of major interest is that all estimates place eukaryote replication units as much smaller than the E. coli replicon (1,100 ju to 1,300 M in length) with a molecular weight of 2.5 x 10 daltons (Cooper and Helmstetter, 1969). 

The eukaryotic somatic cell cycle is defined by a sequential order of tasks a dividing cell has to complete it must replicate its DNA, segregate its chromosomes, grow, and divide. The cell cycle can be divided into four discrete phases. DNA replication is restricted to S phase (DNA synthesis phase), which is preceded by a gap phase called G1 and followed by a gap phase called G2. During mitosis (M phase) the sister chromatids are segregated into two new daughter nuclei and mitosis is completed by the division of the cytoplasm termed cytokinesis (Fig. 1). 

In terms of evolutionary biology, the complex mitotic process of higher animals and plants has evolved through a progression of steps from simple prokaryotic fission sequences. In prokaryotic cells, the two copies of replicated chromosomes become attached to specialized regions of the cell membrane and are separated by the slow intrusion of the membrane between them. In many primitive eukaryotes, the nuclear membrane participates in a similar process and remains intact the spindle microtubules are extranuclear but may indent the nuclear membrane to form parallel channels. In yeasts and diatoms, the nuclear membrane also remains intact, an intranuclear polar spindle forms and attaches at each pole to the nuclear envelope, and a single kinetochore microtubule moves each chromosome to a pole. In the cells of higher animals and plants, the mitotic spindle starts to form outside of the nucleus, the nuclear envelope breaks down, and the spindle microtubules are captured by chromosomes (Kubai, 1975 Heath, 1980 Alberts et al., 1989). 

Abstract. In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase. 

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