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

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DNA Replication, Repair,
and Recombination
chapter
5
The ability of cells to maintain a high degree of order in a chaotic universe depends
upon the accurate duplication of vast quantities of genetic information carried in
chemical form as DNA. This process, called DNA replication, must occur before
a cell can produce two genetically identical daughter cells. Maintaining order
also requires the continued surveillance and repair of this genetic information,
because DNA inside cells is repeatedly damaged by chemicals and radiation from
the environment, as well as by thermal accidents and reactive molecules generated
inside the cell. In this chapter, we describe the protein machines that replicate
and repair the cell’s DNA. These machines catalyze some of the most rapid
and accurate processes that take place within cells, and their mechanisms illustrate
the elegance and efficiency of cell chemistry.
While the short-term survival of a cell can depend on preventing changes
in its DNA, the long-term survival of a species requires that DNA sequences be
changeable over many generations to permit evolutionary adaptation to changing
circumstances. We shall see that despite the great efforts that cells make to protect
their DNA, occasional changes in DNA sequences do occur. Over time, these
changes provide the genetic variation upon which selection pressures act during
the evolution of organisms.
We begin this chapter with a brief discussion of the changes that occur in
DNA as it is passed down from generation to generation. Next, we discuss the cell
mechanisms—DNA replication and DNA repair—that are responsible for minimizing
these changes. Finally, we consider some of the most intriguing pathways
that alter DNA sequences—in particular, those of DNA recombination including
the movement within chromosomes of special DNA sequences called transposable
elements.
In This Chapter
THE MAINTENANCE OF DNA
SEQUENCES
DNA REPLICATION MECHANISMS
THE INITIATION AND
COMPLETION OF DNA
REPLICATION IN CHROMOSOMES
DNA REPAIR
HOMOLOGOUS RECOMBINATION
TRANSPOSITION AND
CONSERVATIVE SITE-SPECIFIC
RECOMBINATION
THE MAINTENANCE OF DNA SEQUENCES
Although, as just pointed out, occasional genetic changes enhance the long-term
survival of a species through evolution, the survival of the individual demands a
high degree of genetic stability. Only rarely do the cell’s DNA-maintenance processes
fail, resulting in permanent change in the DNA. Such a change is called a
mutation, and it can destroy an organism if it occurs in a vital position in the DNA
sequence.
Mutation Rates Are Extremely Low
The mutation rate, the rate at which changes occur in DNA sequences, can be
determined directly from experiments carried out with a bacterium such as Escherichia
coli—a resident of our intestinal tract and a commonly used laboratory
organism (see Figure 1–24). Under laboratory conditions, E. coli divides about
once every 30 minutes, and a single cell can generate a very large population—
several billion—in less than a day. In such a population, it is possible to detect the
small fraction of bacteria that have suffered a damaging mutation in a particular
gene, if that gene is not required for the bacterium’s survival. For example, the
mutation rate of a gene specifically required for cells to use the sugar lactose as an
energy source can be determined by growing the cells in the presence of a different