Maintenance of the accuracy of the DNA genetic
code is critical for both the long- and short-term survival of cells
and species. Sometimes, normal cellular activities, such as duplicating
DNA and making new gametes, introduce
changes or mutations in our DNA.
Other changes are caused by exposure of DNA to chemicals, radiation, or
other adverse environmental conditions. No matter the source, genetic mutations
have the potential for both positive and negative effects on an individual
as well as its species. A positive change results in a slightly different
version of a gene that might eventually prove beneficial in the face of
a new disease or changing environmental conditions. Such beneficial changes
are the cornerstone of evolution. Other mutations are considered deleterious,
or result in damage to a cell or an individual. For example, errors within
a particular DNA sequence may end up either preventing a vital protein from
being made or encoding a defective protein. It is often these types of errors
that lead to various disease states.
The potential for DNA damage is counteracted by a vigorous surveillance
and repair system. Within this system, there are a number of enzymes capable
of repairing damage to DNA. Some of these enzymes are specific for a particular
type of damage, whereas others can handle a range of mutation types. These
systems also differ in the degree to which they are able to restore the
normal, or wild-type, sequence.
Categories of DNA repair
Photoreactivation is the process whereby genetic damage caused
by ultraviolet radiation is reversed by subsequent illumination with
visible or near-ultraviolet light.
Nucleotide excision repair is used to fix DNA lesions, such
as single-stranded breaks or damaged bases, and occurs in stages.
The first stage involves recognition of the damaged region. In the
second stage, two enzymatic reactions serve to remove, or excise,
the damaged sequence. The third stage involves synthesis by DNA polymerase
of the excised nucleotides using the second intact strand of DNA as
a template. Lastly, DNA ligase joins the newly synthesized segment
to the existing ends of the originally damaged DNA strand.
Recombination repair, or post-replication repair, fixes DNA
damage by a strand exchange from the other daughter chromosome. Because
it involves homologous recombination, it is largely error free.
Base excision repair allows for the identification and removal
of wrong bases, typically attributable to deamination – the
removal of an amino group (NH2) – of normal bases as well as
from chemical modification.
Mismatch repair is a multi-enzyme system that recognizes inappropriately
matched bases in DNA and replaces one of the two bases with one that
"matches" the other. The major problem here is recognizing which of
the mismatched bases is incorrect and therefore should be removed
Adaptive/inducible repair describes several protein activities
that recognize very specific modified bases. They then transfer this
modifying group from the DNA to themselves, and, in doing so, destroy
their own function. These proteins are referred to as inducible because
they tend to regulate their own synthesis. For example, exposure to
modifying agents induces, or turns on, more synthesis and therefore
adaptation. SOS repair or inducible error-prone repair is a repair
process that occurs in bacteria and is induced, or switched on, in
the presence of potentially lethal stresses, such as UV irradiation
or the inactivation of genes essential for replication. Some responses
to this type of stress include mutagenesis – the production
of mutations – or cell elongation without cell division. In
this type of repair process, replication of the DNA template is extremely
inaccurate. Obviously, such a repair system must be a desperate recourse
for the cell, allowing replication past a region where the wild-type
sequence has been lost.
Source: National Center
for Biotechnology Information