To form a functional chromosome, a DNA molecule must be able to do more than simply carry genes: it must be able to replicate, and the replicated copies must be separated and reliably partitioned into daughter cells at each cell division. This process occurs through an ordered series of stages, collectively known as the cell cycle, which provides for a temporal separation between the duplication of chromosomes and their segregation into two daughter cells. The cell cycle is briefly summarized in Figure 4–17, and it is discussed in detail in Chapter 17. Briefly, during a long interphase, genes are expressed and chromosomes are replicated, with the two replicas remaining together as a pair of sister chromatids. Throughout this time, the chromosomes are extended and much of their chromatin exists as long threads in the nucleus so that individual chromosomes cannot be easily distinguished. It is only during a much briefer period of mitosis that each chromosome condenses so that its two sister chromatids can be separated and distributed to the two daughter nuclei. The highly condensed chromosomes in a dividing cell are known as mitotic chromosomes (Figure 4–18). This is the form in which chromosomes are most easily visualized; in fact, the images of chromosomes shown so far in the chapter are of chromosomes in mitosis.
Each chromosome operates as a distinct structural unit: for a copy to be passed on to each daughter cell at division, each chromosome must be able to replicate, and the newly replicated copies must subsequently be separated and partitioned
Figure 4–17 A simplified view of the eukaryotic cell cycle. During interphase, the cell is actively expressing its genes and is therefore synthesizing proteins. Also, during interphase and before cell division, the DNA is replicated and each chromosome is duplicated to produce two closely paired sister DNA molecules (called sister chromatids). A cell with only one type of chromosome, present in maternal and paternal copies, is illustrated here. Once DNA replication is complete, the cell can enter M phase, when mitosis occurs and the nucleus is divided into two daughter nuclei. During this stage, the chromosomes condense, the nuclear envelope breaks down, and the mitotic spindle forms from microtubules and other proteins. The condensed mitotic chromosomes are captured by the mitotic spindle, and one complete set of chromosomes is then pulled to each end of the cell by separating the members of each sister-chromatid pair. A nuclear envelope re-forms around each chromosome set, and in the final step of m phase, the cell divides to produce two daughter cells. most of the time in the cell cycle is spent in interphase; m phase is brief in comparison, occupying only about an hour in many mammalian cells.
nuclear envelope surrounding the nucleus INTERPHASE M PHASE INTERPHASE correctly into the two daughter cells. These basic functions are controlled by three types of specialized nucleotide sequences in the DNA, each of which binds specific proteins that guide the machinery that replicates and segregates chromosomes (Figure 4–19).
Experiments in yeasts, whose chromosomes are relatively small and easy to manipulate, have identified the minimal DNA sequence elements responsible for each of these functions. One type of nucleotide sequence acts as a DNA replication origin, the location at which duplication of the DNA begins. Eukaryotic chromosomes contain many origins of replication to ensure that the entire chromosome can be replicated rapidly, as discussed in detail in Chapter 5.
After DNA replication, the two sister chromatids that form each chromosome remain attached to one another and, as the cell cycle proceeds, are condensed further to produce mitotic chromosomes. The presence of a second specialized DNA sequence, called a centromere, allows one copy of each duplicated and condensed chromosome to be pulled into each daughter cell when a cell divides. A protein complex called a kinetochore forms at the centromere and attaches the duplicated chromosomes to the mitotic spindle, allowing them to be pulled apart (discussed in Chapter 17).