Are there different repair pathways for specific types of DNA damage?

Yes, there are different repair pathways for specific types of DNA damage. DNA damage can arise due to various factors such as UV radiation, chemicals, and errors during DNA replication. In order to maintain the integrity of the genome, cells have evolved different mechanisms to repair different types of DNA damage.

Types of DNA Damage and Repair Pathways

There are several types of DNA damage, and each type is repaired by specific repair pathways. Some of the major types of DNA damage and their corresponding repair pathways include:

  • Thymine dimers: Thymine dimers are caused by exposure to UV radiation. They are repaired by the nucleotide excision repair (NER) pathway.
  • Double-strand breaks: Double-strand breaks can be caused by ionizing radiation or chemicals. They are repaired by homologous recombination (HR) or non-homologous end joining (NHEJ) pathways.
  • Base excision repair (BER): BER is responsible for repairing damaged bases that are caused by oxidative stress or alkylating agents.
  • Mismatch repair (MMR): MMR corrects errors that occur during DNA replication, such as mismatched bases.
  • Direct reversal: Some DNA damage can be repaired by direct reversal mechanisms, such as photolyase that repairs UV-induced lesions.

Nucleotide Excision Repair (NER)

NER is a highly versatile repair pathway that is responsible for removing a wide range of DNA lesions, including thymine dimers caused by UV radiation. The NER pathway involves the following steps:

  • Recognition of the damaged DNA by a protein complex.
  • Incision of the damaged strand on either side of the lesion.
  • Removal of the damaged segment by a helicase.
  • Synthesis of a new DNA strand by DNA polymerase.
  • Ligation of the newly synthesized DNA strand to the original strand.
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Homologous Recombination (HR) and Non-homologous End Joining (NHEJ)

Double-strand breaks are among the most lethal forms of DNA damage, and cells have evolved two main pathways to repair them:

  • Homologous recombination (HR): HR is a high-fidelity repair pathway that uses a homologous DNA template to repair double-strand breaks. This pathway is important during the S and G2 phases of the cell cycle.
  • Non-homologous end joining (NHEJ): NHEJ is an error-prone repair pathway that directly joins the broken ends of DNA strands. This pathway is active throughout the cell cycle but is more predominant in non-dividing cells.

Base Excision Repair (BER)

BER is a critical repair pathway that corrects damaged bases in DNA. The BER pathway involves the following steps:

  • Recognition of the damaged base by a DNA glycosylase enzyme.
  • Removal of the damaged base by the DNA glycosylase, creating an abasic site.
  • Cleavage of the abasic site by an AP endonuclease.
  • Filling in the gap with the correct nucleotide by DNA polymerase.
  • Ligation of the newly synthesized DNA strand.

Mismatch Repair (MMR)

MMR is a crucial repair pathway that corrects errors that occur during DNA replication, such as mismatched bases. The MMR pathway involves the following steps:

  • Recognition of the mismatch by the MMR machinery.
  • Excision of the incorrect nucleotide by an exonuclease.
  • Resynthesis of the correct DNA sequence by DNA polymerase.
  • Ligation of the newly synthesized DNA strand.

Direct Reversal Mechanisms

Some DNA damage can be repaired by direct reversal mechanisms, which involve the direct removal of the damaged base or lesion without the need for nucleotide excision or synthesis. Examples of direct reversal mechanisms include:

  • Photolyase: Photolyase is an enzyme that repairs UV-induced lesions by directly reversing the damage caused by UV radiation.
  • Alkyltransferases: Alkyltransferases are a class of enzymes that directly remove alkyl groups from DNA bases.
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