DNA Repair

Repair During DNA Replication

  • DNA Polymerase III possess the ability to proofread replication errors which works during the process of DNA replication. This is performed via 3′ to 5′ exonuclease activity. DNA Polymerase III reverses a mismatched base by backing up and replacing the nucleotide.
  • The polymerase that replacing the RNA primers with DNA can also replace incorrect nucleotide placement with 5′ to 3′ activity. Note: there is no 3′-5′ activity on this polymerase.

Repair of Mutations

Despite the proofreading ability of certain polymerases, mutations can still arise as a result of DNA replication. Additionally, many environmental and even entirely random factors can lead to DNA mutations.  The remainder of this unit discusses the different processes of mutation repair.

Direct Reversal

Allows for direct repair of DNA damage. Generally able to repair pyrimidine dimers caused by UV radiation which can lead to skin cancer if left damaged. This method does not work on irreversible damage, during which other mechanisms must be used.

The figure below shows a graphical representation of the formation of a pyrimidine dimer.

By derivative work: Mouagip (talk) DNA_UV_mutation.gif: NASA/David Herring This vector graphics image was created with Adobe Illustrator. (DNA_UV_mutation.gif) [Public domain], via Wikimedia Commons

Mismatch Repair

  • Homology Dependent: Requires the intact information from the complementary strand of the damaged DNA strand to repair.

Incorrectly paired bases are detected, cut out, and replaced by DNA Polymerase. It can be difficult to identify which base is correct versus incorrect. Prokaryotes and eukaryotes have different mechanisms which can vary more so between different species to detect the parent strand (correct base) versus the newly synthesized strand (incorrect base).

  • Most prokaryotes use methylation patterns to distinguish parent vs daughter strands. The daughter strands usually have not been methylated and can thus be identified.
  • Another mechanisms used by most eukaryotes and some prokaryotes is detection of gaps between Okazaki fragments or the free 3′ end on the newly synthesized strand.

Nucleotide Excision Repair

  • Homology Dependent: Requires the intact information from the complementary strand of the damaged DNA strand to repair.

Nucleotide excision repair involves the cuttong of nucleotides that have been damaged and/or are defective and replacement via DNA polymerase. This process generally involved damaged nucleotides that could not be directly reversed such as thymine dimers. (refer to pyrimidine dimer figure above).

Base Excision Repair

  • Homology Dependent: Requires the intact information from the complementary strand of the damaged DNA strand to repair.

The base and its sugar phosphate backbone is cut out via endonuclease activity and then the removed bases are resynthesized by DNA polymerase.

Double-Stranded Repair

Double stranded breaks have different mechanisms required to repair them. There are two mechanisms, both sharing the end goal of fusing together chromosomes that have broken apart.

Homologous Recombination

Right after DNA replication, sister chromatids can be identified. Thus, if there is a double-stranded break during this time period, the sister chromatid can be used to help repair the break. This method is essentially error-free.

Click here for an excellent animation illustrating Homologous Recombination.

Nonhomologous End Joining

This process is a last resort and stitches together broken chromosomes, whether homologous or not. This occurs in cells that are not actively dividing, therefore do not have the opportunity to identify and use the sister chromatids. Therefore, this method is highly prone to error.

Summary

The following table summarizes some important information about mutations and their repair mechanisms (Note: direct reversal and proofreading mechanisms are not listed). It is important to understand the general repair mechanisms and when they are used.

Mutation Cause  Mutation Effect Repair Mechanism
Replication Error A-G or T-C mismatch Mismatch Repair
Free Radicals
X-Ray
Alkylating Agents
Abasic Sites
DNA Base modifications
Single Strand DNA
Base Excision Repair
UV Radiation Pyrimidine Photodimers Nucleotide Excision Repair
X-Ray
Antitumor Agents
Interstrand Crosslinks
Double-Stranded Breaks
Homologous or Nonhomologous Recombination

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