524
chapter 23
Structure and Properties of DNA
Tautomerization of the bases can occur as the free base
and as polynucleotides. If tautomerization of a base should
occur at the moment of replication of that region of DNA,
an incorrect base may be inserted. For example, the tau-
tomeric form of adenine can pair with cytosine or the tau-
tomeric form of thymine can pair with guanine. During
subsequent rounds of DNA replication these mismatched
base pairs can result in point mutations in half of the DNA
molecules in subsequent cycles of DNA replication and
cell divisions. During replication, tautomerization of bases
in DNA and ensuing mistakes in base pairing are extremely
rare, but experiments show that point mutations do arise
in this manner and contribute to genetic variation. How-
ever, most mistakes in base pairing that occur during DNA
replication are corrected by enzymatic editing or repair
functions.
Méthylation of Bases
After the four bases have been incorporated into DNA, they
can be modified by
méthylation,
the addition of methyl
groups at various positions (Figure 23-5). The bases that
are most frequently methylated are guanine and cytosine.
Méthylation of cytosine residues influences gene regu-
lation in higher organisms, and about 70% of GC base
pairs in mammalian cells are methylated. The pattern of
méthylation of cytosine residues is inherited and is specific
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F I G U R E 2 3 -5
Methyl groups can be added to bases in DNA. Except for some yeasts and
insects, all DNA contains methylated bases. The attachment of methyl
groups to bases at specific sequences in DNA acts to regulate the functions
of DNA. One function of site-specific méthylation in prokaryotes is to
protect endogenous bacterial DNA from digestion by restriction
endonucleases produced by the bacteria.
for each species. However, méthylation of DNA is not uni-
versal; for example, the DNA in the fruitfly
D rosoph ilia
is completely unmethylated.
Méthylation of DNA is primarily the result of two en-
zymes,
Dam methylase
and
Dem methylase.
Dam methy-
lase transfers a methyl group from S-adenosylmethionine
to an adenine contained in any GATC sequence in DNA.
Dem methylase acts in a similar fashion on cytosine
residues in the sequence CCAGG. One or both cytosines
in opposite strands of DNA are methylated. Methylated
segments of DNA are recognized by proteins that interact
with DNA in such processes as replication, recombination,
and gene expression. Méthylation of DNA also serves an
important function in bacteria. Méthylation of specific se-
quences in bacterial DNA protects the bacterial DNA from
cleavage by endogenously synthesized restriction endonu-
cleases.
Many human genes are methylated differently in ma-
ternal and paternal chromosomes at CpG nucleotides, a
mechanism that is referred to as
imprinting.
As a result of
genomic imprinting, the expression of genes on maternal
and paternal chromosomes differs; the loss of imprinting
through mutation or some other mechanism can result in
overexpression of critical genes and severe disease. Two
inherited diseases that are the result of faulty imprint-
ing are
P rader-W illi/A n gelm an n ’s syndrom e (PW S)
and
B eckw ith-W iedem ann syndrom e (BW S).
The symptoms of
PWS include neonatal hypotonia, hypogonadism, obesity,
and short stature; the symptoms of BWS are omphalocele
(abdominal wall defect), thickening of long bones, and
renal abnormalities.
The altered gene in BWS codes for insulin-like growth
factor-2 (
IG F 2
) and is located on the short arm of chro-
mosome 15. Usually
IG F 2
is silent in the maternal chro-
mosome and active in the paternal chromosome. In some
cases of BWS, the child receives two copies of chromo-
some 15 from the father, a condition knows as
disomy.
These individuals have twice the normal level of IGF2 and
suffer from “overgrowth.” Low levels of IGF2 may also
result from disomy and lead to abnormal “undergrowth.”
Other inherited diseases and cancers may result from mu-
tations that affect imprinting and normal transmission of
chromosomes (Chapter 26).
23.2 Physical and Chemical Structure of DNA
The Watson-Crick DNA Structure
In DNA, two polydeoxynucleotide strands are coiled about
one another in a double-helical structure as originally
proposed by the Watson-Crick (W-C) model (Figure 23-6).
The important features of the W-C model are as follows:
