Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

186 Chapter 4: DNA, Chromosomes, and Genomes
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).
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.
1 µm
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 MBoC6 Terry m4.20/4.18
D. Allen.)
telomere
replication
origin
centromere
INTERPHASE
replicated
chromosome
MITOSIS
portion of
mitotic spindle
CELL
DIVISION
INTERPHASE
+
duplicated
chromosomes
in separate
daughter cells
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.