Most of the mistakes during DNA replication are promptly corrected by DNA polymerase. DNA polymerase proofreads the base that has just been added. In proofreading, the DNA pol reads the newly-added base before adding the next one so a correction can be made. The polymerase checks whether the newly-added base has paired correctly with the base in the template strand. If it is the correct 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 incorrect nucleotide. This is performed by the exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, a new one will be added again.

Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair. 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. The DNA polymerase is able to remove the incorrectly-incorporated bases from the newly-synthesized, strand.

In another type of repair mechanism, nucleotide excision repair, enzymes replace incorrect bases by making a cut on both the 3′ and 5′ ends of the incorrect base. The segment of DNA is removed and replaced with the correctly-paired nucleotides by the action of DNA pol. 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.

Practice Questions

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Molecular targets of antiretroviral therapies

MCAT Official Prep (AAMC)

Key Points

• DNA polymerase enzyme proofreads the nucleotides added to the new strand of the DNA during replication.
• An incorrect nucleotide is removed by the exonuclease activity of DNA polymerase and a new nucleotide is added.
• Mismatch repair enzymes recognize incorrectly incorporated bases due to mutation, remove them from DNA, and replace them with the correct bases.
• In nucleotide excision repair, enzymes remove incorrect bases with a few surrounding bases. These are replaced with the correct bases with the help of a DNA polymerase and the template DNA.
• When replication mistakes are not corrected, they may result in mutations, which sometimes can have serious consequences.

Key Terms

• DNA polymerase: An enzyme that adds the nucleotides during replication of the DNA.
• exonuclease: An enzyme that removes or cleaves the nucleotide
• mismatch repair: a system for recognizing and repairing some forms of DNA damage and erroneous insertion, deletion, or misincorporation of bases that can arise during DNA replication and recombination
• nucleotide excision repair: a DNA repair mechanism that corrects damage done by UV radiation, including thymine dimers and 6,4 photoproducts that cause bulky distortions in the DNA
• mutation: the errors or mistakes in the DNA either due to errors in replication, due to environmental factors like UV light or due to natural reactions in the body.