The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added.
If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. Once the incorrect nucleotide has been removed, a new one will be added again. Figure 1. Proofreading by DNA polymerase corrects errors during replication.
Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair Figure 2.
The enzymes recognize the incorrectly added nucleotide and excise it; this is then replaced by the correct base. If this remains uncorrected, it may lead to more permanent damage. How do mismatch repair enzymes recognize which of the two bases is the incorrect one? Thus, DNA polymerase is able to remove the wrongly incorporated bases from the newly synthesized, non-methylated strand.
How do mismatch repair enzymes recognize which of the two bases is the incorrect one? Thus, DNA polymerase is able to remove the wrongly incorporated bases from the newly synthesized, non-methylated strand. In eukaryotes, the mechanism is not very well understood, but it is believed to involve recognition of unsealed nicks in the new strand, as well as a short-term continuing association of some of the replication proteins with the new daughter strand after replication has completed.
Another type of repair mechanism, nucleotide excision repair , is similar to mismatch repair, except that it is used to remove damaged bases rather than mismatched ones. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase.
This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers. A well-studied example of mistakes not being corrected is seen in people suffering from xeroderma pigmentosa Figure. Affected individuals have skin that is highly sensitive to UV rays from the sun. When individuals are exposed to UV light, pyrimidine dimers, especially those of thymine, are formed; people with xeroderma pigmentosa are not able to repair the damage.
These are not repaired because of a defect in the nucleotide excision repair enzymes, whereas in normal individuals, the thymine dimers are excised and the defect is corrected.
Mutations , variations in the nucleotide sequence of a genome, can also occur because of damage to DNA. Such mutations may be of two types: induced or spontaneous. Induced mutations are those that result from an exposure to chemicals, UV rays, x-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent; they are a result of natural reactions taking place within the body.
Mutations may have a wide range of effects. Point mutations are those mutations that affect a single base pair. The most common nucleotide mutations are substitutions, in which one base is replaced by another. These substitutions can be of two types, either transitions or transversions.
Transition substitution refers to a purine or pyrimidine being replaced by a base of the same kind; for example, a purine such as adenine may be replaced by the purine guanine. Transversion substitution refers to a purine being replaced by a pyrimidine, or vice versa; for example, cytosine, a pyrimidine, is replaced by adenine, a purine.
Some point mutations are not expressed; these are known as silent mutations. Silent mutations are usually due to a substitution in the third base of a codon, which often represents the same amino acid as the original codon. Other point mutations can result in the replacement of one amino acid by another, which may alter the function of the protein.
Point mutations that generate a stop codon can terminate a protein early. Some mutations can result in an increased number of copies of the same codon. These are called trinucleotide repeat expansions and result in repeated regions of the same amino acid. Mutations can also be the result of the addition of a base, known as an insertion, or the removal of a base, also known as deletion.
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