The third specialized DNA sequence forms telomeres, the ends of a chromosome. Telomeres contain repeated nucleotide sequences that enable the ends of chromosomes to be efficiently replicated. Telomeres also perform another function: the repeated telomere DNA sequences, together with the regions adjoining them, form structures that protect the end of the chromosome from being mistaken by the cell for a broken DNA molecule in need of repair. We discuss both this type of repair and the structure and function of telomeres in Chapter 5.
In yeast cells, the three types of sequences required to propagate a chromosome are relatively short (typically less than 1000 base pairs each) and therefore use only a tiny fraction of the information-carrying capacity of a chromosome. Although telomere sequences are fairly simple and short in all eukaryotes, the DNA sequences that form centromeres and replication origins in more complex organisms are much longer than their yeast counterparts. For example, experiments suggest that a human centromere can contain up to a million nucleotide pairs and that it may not require a stretch of DNA with a defined nucleotide sequence. Instead, as we shall discuss later in this chapter, a human centromere is thought to consist of a large, regularly repeating protein–nucleic acid structure that can be inherited when a chromosome replicates.
Figure 4–18 A mitotic chromosome.
A mitotic chromosome is a condensed duplicated chromosome in which the two new chromosomes, called sister chromatids, are still linked together (see Figure 4–17). The constricted region indicates the position of the centromere. (Courtesy of Terry D. Allen.)
Figure 4–19 The three DNA sequences required to produce a eukaryotic chromosome that can be replicated and then segregated accurately at mitosis.
Each chromosome has multiple origins of replication, one centromere, and two telomeres. Shown here is the sequence of events that a typical chromosome follows during the cell cycle. The DNA replicates in interphase, beginning at the origins of replication and proceeding bidirectionally from the origins across the chromosome. In m phase, the centromere attaches the duplicated chromosomes to the mitotic spindle so that a copy of the entire genome is distributed to each daughter cell during mitosis; the special structure that attaches the centromere to the spindle is a protein complex called the kinetochore (dark green). The centromere also helps to hold the duplicated chromosomes together until they are ready to be moved apart. The telomeres form special caps at each chromosome end.
All eukaryotic organisms have special ways of packaging DNA into chromosomes. For example, if the 48 million nucleotide pairs of DNA in human chromosome 22 could be laid out as one long perfect double helix, the molecule would extend for about 1.5 cm if stretched out end to end. But chromosome 22 measures only about 2 μm in length in mitosis (see Figures 4–10 and 4–11), representing an endto-end compaction ratio of over 7000-fold. This remarkable feat of compression is performed by proteins that successively coil and fold the DNA into higher and higher levels of organization. Although much less condensed than mitotic chromosomes, the DNA of human interphase chromosomes is still tightly packed.
In reading these sections it is important to keep in mind that chromosome structure is dynamic. We have seen that each chromosome condenses to an extreme degree in the M phase of the cell cycle. Much less visible, but of enormous interest and importance, specific regions of interphase chromosomes decondense to allow access to specific DNA sequences for gene expression, DNA repair, and replication—and then recondense when these processes are completed. The packaging of chromosomes is therefore accomplished in a way that allows rapid localized, on-demand access to the DNA. In the next sections, we discuss the specialized proteins that make this type of packaging possible.
Nucleosomes Are a basic Unit of Eukaryotic Chromosome Structure