CHAPTER
DNA Replication, Repair,
and Mutagenesis
DNA is the permanent repository for all genetic informa-
tion in every cell and, as such, must maintain the fidelity
of that information from one cell generation to the next
as well as from one human generation to the next. This
means, in the case of human beings, accurately copying
the approximately
6
x
1 0 9
base pairs in each diploid cell
prior to its undergoing mitosis (somatic cells) or meiosis
(germ cells).
Over billions of years of biological history, cells have
developed intricate mechanisms to ensure faithful replica-
tion of DNA molecules and for the detection and repair of
errors in the sequence of bases when they do occur. How-
ever, errors
must
occur; the evolution of new organisms
and new species depends on a supply of new genomes, the
source of genetic diversity on which natural selection acts
and which fuels biological evolution. This is the paradox
of DNA replication. On the one hand, DNA must replicate
itself with the utmost accuracy; on the other hand, it must
allow a low frequency of genetic change to occur dur-
ing each round of replication, particularly during meiosis,
which produces the cells (sperm and ova) that pass DNA
to succeeding generations.
This apparent paradox is resolved by the mechanisms
of mutation and recombination that provide for a small
but essential amount of genetic change to occur in each
generation. Mutations occur spontaneously during DNA
replication because not all of the replication errors or dam-
age to templates are detected and repaired by the enzymes
responsible for proofreading and repairing DNA. The rate
of mutations can be markedly increased by ionizing radi-
ation (x-rays), mutagenic chemicals (cigarette smoke), or
retroviruses that integrate in DNA (HIV). Thus, mutations
are essential to the species because they allow for adaptive
changes but often are harmful to the individual by giving
rise to cells that cause cancer, congenital defects, and other
diseases.
Recombination occurs primarily in germ cells of eukar-
yotes and during cell division in partially diploid prokary-
otes. In general, recombination does not occur in mitosis
of eukaryotic cells. However, recombination is an integral
part of meiosis in which recombinant sperm and ova pro-
vide new genotypes and phenotypes in each generation
which may be favored by natural selection.
In this chapter, the basic mechanisms of DNA replica-
tion, recombination, repair, and mutation are discussed.
Much of our understanding of these mechanisms derived
from the study of bacteria. However, as further evidence
for the unity of biology, the processes that replicate and
modify DNA in bacteria also apply to human DNA with
some modifications.
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