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

268 Chapter 5: DNA Replication, Repair, and Recombination
human cell loses about 18,000 purine bases (adenine and guanine) every day
because their N-glycosyl linkages to deoxyribose hydrolyze, a spontaneous reaction
called depurination. Similarly, a spontaneous deamination of cytosine to
uracil in DNA occurs at a rate of about 100 bases per cell per day (Figure 5–38).
DNA bases are also occasionally damaged by an encounter with reactive metabolites
produced in the cell, including reactive forms of oxygen and the high-energy
methyl donor S-adenosylmethionine, or by exposure to chemicals in the
environment. Likewise, ultraviolet radiation from the sun can produce a covalent
linkage between two adjacent pyrimidine bases in DNA to form, for example,
thymine dimers (Figure 5–39). If left uncorrected when the DNA is replicated,
most of these changes would be expected to lead either to the deletion of one or
more base pairs or to a base-pair substitution in the daughter DNA chain (Figure
5–40). The mutations would then be propagated throughout subsequent cell generations.
Such a high rate of random changes in the DNA sequence would have
disastrous consequences.
The DNA Double Helix Is Readily Repaired
The double-helical structure of DNA is ideally suited for repair because it carries
two separate copies of all the genetic information—one in each of its two strands.
Thus, when one strand is damaged, the complementary strand retains an intact
copy of the same information, and this copy is generally used to restore the correct
nucleotide sequences to the damaged strand.
An indication of the importance of a double-strand helix to the safe storage of
genetic information is that all cells use it; only a few small viruses use single-strand
DNA or RNA as their genetic material. The types of repair processes described in
this section cannot operate on such nucleic acids, and once damaged, the chance
of a permanent nucleotide change occurring in these single-strand genomes of
viruses is thus very high. It seems that only organisms with tiny genomes (and
therefore tiny targets for DNA damage) can afford to encode their genetic information
in any molecule other than a DNA double helix.
GUANINE
DEPURINATION
O
DEAMINATION
O
P
O _
H
O CH 2
O
N
N
O
H
N
H
N N
H
CYTOSINE
H H
N
H
N
H
H 2 O
O
N N
N N
H
GUANINE
H 2 O
H
N
H
H
O
O
P
O _
O CH 2
O
sugar phosphate after
depurination
OH
H
URACIL
O
N
H
O
H
N
O
O
H
N
O
O
P
O _
O CH 2
O
NH 3
O
P
O _
O CH 2
O
DNA
strand
DNA
strand
Figure 5–38 Depurination and deamination. These reactions are two of the most frequent spontaneous chemical reactions that create serious
DNA damage in cells. Depurination can release guanine (shown here), as well as adenine, from DNA. The major type of deamination reaction
converts cytosine to an altered DNA base, uracil (shown here), but deamination occurs on other bases as well. These reactions normally take place
in double-helical DNA; for convenience, only one strand is shown.
MBoC6 m5.45/5.39