Chromosome Duplication And Segregation

Eukaryotic Chromosomes Require Centromeres, Telomeres, and Origins of Replication to Be Maintained During Celt Division

There are several important DNA elements in eukaryotic: chromosomes that are not genes and are not involved in regulating the expression of genes (Figure 7-6). These elements include origins of replication that direct the duplication of the chromosomal DNA, centromeres that act as "handles" for the movement of chromosomes into daughter cells, and telomeres that protect and replicate the ends of linear chromosomes. Al! these features are critical for the proper duplication and segregation of the chromosomes during cell division. We now look at each of these elements in more detail.

Origins of replication are the sites at which the DNA replication machinery assembles to initiate replication. They are found some 30—40 kb apart throughout the length of each eukaryotic chromosome. Prokaryotic chromosomes also require origins of replication. Unlike their eukaryotic counterparts, prokaryotic chromosomes typically have

DNA replication mitosis

FIGURE 7-6 Centromeres, origins of the replication, and telomeres are required for eukaryotic chromosome maintenance. Each eukaryotic chromosome indudes two telomeres, one centromere, and many origins of replication telomeres are located at each end of each chromosome. Unlike telomeres, the sin-gle centromere found on each chromosome is not in a defined position. Some centromeres are near the middle of the chromosome and others are closer to a telomere. Origins of replication are located throughout the length of each chromosome (approximately every 30 kb in the budding yeast S. cerevisiae).

DNA replication mitosis

FIGURE 7-6 Centromeres, origins of the replication, and telomeres are required for eukaryotic chromosome maintenance. Each eukaryotic chromosome indudes two telomeres, one centromere, and many origins of replication telomeres are located at each end of each chromosome. Unlike telomeres, the sin-gle centromere found on each chromosome is not in a defined position. Some centromeres are near the middle of the chromosome and others are closer to a telomere. Origins of replication are located throughout the length of each chromosome (approximately every 30 kb in the budding yeast S. cerevisiae).

only a single site of replication initiation. In general, origins of replication are found in noncoding regions. The DNA sequences that are recognized as origins of replication are discussed in detail in Chapter 8.

Centromeres are required for the correct segregation of the chromosomes after DNA replication. The two copies of each replicated chromosome are called daughter chromosomes and they must be separated with one copy going to each of the two daughter cells. Like origins of replication, centromeres direct the formation of an elaborate protein complex, in this case, called a kinelochore. The kinetochore interacts with the machinery that pulls the daughter chromosomes away from one another and into the two daughter cells. In contrast to the many origins of replication found on each eukaryotic chromosome, it is critical that each chromosome has one and only one centromere (Figure 7-7a). In the absence of a centromere, the replicated chromosomes segregate randomly, leading to frequent loss or duplication of chromosomes (Figure 7-7b). If present in multiple copies, centromeres can cause a single chromosome to be pulled into both daughter cells, leading to chromosome breakage (Figure 7-7c). Centromeres vary greatly in size. In Ihe yeas! S. cerevisiae, centromeres are less than 200 bp. In contrast, in the majority of enkaryotes, centromeres are >40 kb and are composed of largely repetitive DNA sequences (Figure 7-8).

Telomeres arc located at the two ends of a linear chromosome. Like origins of replication and centromeres, telomeres are bound by a number of proteins. In this case, the proteins perform two important functions.

First, telomeric proteins distinguish the natural ends of the chromosome from sites of chromosome breakage and other DNA breaks in c two centromeres

FIGURE 7-7 More or less than one centromere leads to chromosome loss or breakage.

(a) Normal chromosomes have one centromere. After replication of a chromosome, each copy of the centromere directs the formation of a kinetochore. These two kinetochores then bind to opposite poles of the mitotic spindle and are pulled into the opposite sides of the cell priot to cell division (b) Chromosomes lacking centromeres are rapidly lost from ceils, in the absence of the centromere, the chromosomes do not attach to the spindle and are randomly distributed to the two daughter cells. This leads to frequent events in which one daughter gets two copies of a chromosome and the other daughter cell is mtssing the same chromosome, (c) Chromosomes with two or more centromeres are frequently broken during segregation. If a chromosome has more than one centromere, it can be bound simultaneously to both poles ot the mitotic spindle. When segregation is initiated, the opposing forces of the mitotic spindle frequently break chromosomes attached to both poles.

a one centromere

one chromosome for each cell b no centromeres random segregation of chromosome a one centromere b no centromeres one chromosome for each cell c two centromeres random segregation of chromosome chromosome breakage (due to more than one centromere)

FIGURE 7-7 More or less than one centromere leads to chromosome loss or breakage.

(a) Normal chromosomes have one centromere. After replication of a chromosome, each copy of the centromere directs the formation of a kinetochore. These two kinetochores then bind to opposite poles of the mitotic spindle and are pulled into the opposite sides of the cell priot to cell division (b) Chromosomes lacking centromeres are rapidly lost from ceils, in the absence of the centromere, the chromosomes do not attach to the spindle and are randomly distributed to the two daughter cells. This leads to frequent events in which one daughter gets two copies of a chromosome and the other daughter cell is mtssing the same chromosome, (c) Chromosomes with two or more centromeres are frequently broken during segregation. If a chromosome has more than one centromere, it can be bound simultaneously to both poles ot the mitotic spindle. When segregation is initiated, the opposing forces of the mitotic spindle frequently break chromosomes attached to both poles.

the cell. Ordinarily, DNA ends are the sites of frequent recombination and DNA degradation. The proteins that assemble at telomeres form a structure that is resistant to both of these events.

Second, telomeres act as a specialized origin of replication thai allows the cell to replies to the ends of the chromosomes. For reasons that will be described in detail in Chapter 8, the standard DNA replication machinery cannot completely replicate the ends of a linear chromosome. Telomeres facilitate end replication through the recruitment of an unusual DNA polymerase called telomerase.

In contrast to most of the chromosome, a substantial portion of the telomere is maintained in a single-stranded form (Figure 7-9). Most telomeres have a simple repeating sequence thai varies from organ-

_125 bp

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  • Nadine Jung
    What is centromere duplication?
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