Biology Reference
In-Depth Information
Two types of damage, DNA damaged caused by UV light and modifications
of G by the addition of methyl or ethyl groups to the sixth oxygen position of
the purine ring, are repaired directly (
direct repair
) (
Cooper 2000
). The most
common repair mechanism in cells involves removal (excision) of damaged com-
ponents of the DNA. Repair can be divided into the following excision repair
systems: base-excision repair, nucleotide-excision repair, and mismatch repair.
Base-excision
repair involves removal of only the damaged base from the DNA
strand.
Nucleotide-excision
repair operates mainly on damage caused by envi-
ronmental mutagens and involves DNA synthesis and ligation to replace an
excised oligonucleotide (
Lindahl and Wood 1999
). In
mismatch repair
, the mis-
matched bases that are incorporated during replication occasionally are not
removed by the proofreading activity of DNA polymerase. The mismatched
bases that are not removed are corrected by the mismatch repair system. If the
DNA is not repaired before replication by the above-mentioned mechanisms, a
postreplication repair system comes into play.
Postreplication repair
(recombi-
national repair) can repair several types of damage to DNA, including double-
strand breaks introduced into DNA by irradiation.
1.22 Mutations in the Genome
Changes in the genetic material (
genotype
) of an organism occur if DNA repair
is not successful. Such changes are
mutations
. Many kinds of mutations can
occur: within an exon, within introns, or in the chromosomal regions (
inter-
genic regions
) located between the genes. If a mutation occurs in an intergenic
region, it may be silent and have no detectable effect on the cell or individual.
If a mutation occurs in an exon, it may alter protein product and cause a change
in the organism's
phenotype
(or appearance). A mutation in an intron may not
have an effect on the phenotype, but it could have an effect if there are regula-
tory elements in the intron that are important for proper gene function.
An organism with the “normal” appearance (phenotype) for that species is
called the “
wild type
,” whereas an organism with a phenotype that has been
changed is a
mutant
. If the mutation is
dominant
(meaning that only a single
copy is required to cause the change in phenotype), the name of the gene is
capitalized. If the mutation is
recessive
(meaning that both copies of the gene
carry the mutation), the name is not capitalized.
A
mutagen
is a chemical or physical agent that causes changes in bases.
Mutagens include UV radiation, X-irradiation, ethyl methane sulfonate, base
analogs such as 5-bromouracil, acridine dyes, and nitrous acid. Mutations occur
spontaneously approximately once in every 10
8
bp/cell division, or they can be
induced by the experimenter.
