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DNA Replication, Repair,  and Recombination
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.
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.
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 sugar, such as glucose, and testing them subsequently to see how many have lost the ability to survive on a lactose diet. The fraction of damaged genes underestimates the actual mutation rate because many mutations are silent (for example, those that change a codon but not the amino acid it specifies, or those that change an amino acid without affecting the activity of the protein coded for by the gene). After correcting for these silent mutations, one finds that a single gene that encodes an average-sized protein (~103 coding nucleotide pairs) accumulates a mutation (not necessarily one that would inactivate the protein) approximately once in about 106 bacterial cell generations. Stated differently, bacteria display a mutation rate of about three nucleotide changes per 1010 nucleotides per cell generation.