Page 265 - Color Atlas of Biochemistry

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256 Molecular genetics

Mutation and repair B. Effects
Nitrous acid causes point mutations (1). For
Genetic information is set down in the base
sequence of DNA. Changes in the DNA bases example, C is converted to U, which in the
next replication pairs with A instead of G.
or their sequence therefore have mutagenic
effects. Mutagens often also damage growth The alteration thus becomes permanent. Mu-
tations in which a number of nucleotides not
regulation in cells, and they are then also
carcinogenic (see p. 400). Gene alterations divisible by three are inserted or removed
lead to reading errors in whole segments of
(mutations)are one of the decisive positive
factors in biological evolution. On the other DNA, as they move the reading frame (frame-
hand, an excessive mutation frequency would shift mutations). This is shown in Fig. 2 using
a simple example. From the inserted C on-
threaten the survival of individual organisms
or entire species. For this reason, every cell wards, the resulting mRNA is interpreted dif-
ferently during translation, producing a com-
has repair mechanisms that eliminate most of
the DNA changes arising from mutations (C). pletely new protein sequence.

C. Repair mechanisms
A. Mutagenic agents
An important mechanism for the removal of
Mutations can arise as a result of physical or DNA damage is excision repair (1). In this
chemical effects, or they can be due to acci-
dental errors in DNA replication and recombi- process, a specific excision endonuclease re-
moves a complete segment of DNA on both
nation.
sides of the error site. Using the sequence of
The principal physical mutagen is ionizing
radiation (α, β,and γ radiation, X-rays). In the opposite strand, the missing segment is
then replaced by a DNA polymerase. Finally, a
cells, it produces free radicals (molecules
with unpaired electrons), which are ex- DNA ligase closes the gaps again.
Thymine dimers can be removed by
tremely reactive and can damage DNA.
Short-wavelength ultraviolet light (UV light) photoreactivation (2). A specific photolyase
also has mutagenic effects, mainly in skin cells binds at the defect and, when illuminated,
(sunburn). The most common chemical cleaves the dimertoyield twosingle bases
change due to UV exposure is the formation again.
of thymine dimers, in which two neighboring A third mechanism is recombination repair
thymine bases become covalently linked to (3, shown in simplified form). In this process,
one another (2). This results in errors when the the defect is omitted during replication. The
gap is closed by shifting the corresponding
DNA is readduringreplication andtranscription.
sequence from the correctly replicated second
Only a few examples of the group of chem- strand. The new gap that results is then filled
ical mutagens are shown here. Nitrous acid
(HNO 2 ;salt: nitrite) and hydroxylamine by polymerases and ligases. Finally, the orig-
(NH 2 OH) both deaminate bases; they convert inal defect is corrected by excision repair as in
Fig. 1 (not shown).
cytosine to uracil and adenine to inosine.
Alkylating compounds carry reactive
groups that can form covalent bonds with
DNA bases (see also p. 402). Methylnitro-
samines (3) release the reactive methyl cation
+
(CH 3 ), which methylates OH and NH 2 groups
in DNA. The dangerous carcinogen benzo
[a]pyrene is an aromatic hydrocarbon that is
only converted into the active form in the
organism (4;see p. 316). Multiplehydroxyla-
tion of one of the rings produces a reactive
epoxide that can react with NH 2 groups in
guanine residues, for example. Free radicals
of benzo[a ]pyrene also contribute to its tox-
icity.

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