Key DNA Repair Mechanisms

DNA repair mechanisms are vital for maintaining genetic stability and preventing mutations. These processes, including Base Excision Repair and Nucleotide Excision Repair, ensure that our DNA remains intact despite damage from environmental factors and replication errors.

1. Base Excision Repair (BER)

   • Targets and repairs small, non-helix-distorting base lesions in DNA.
   • Involves DNA glycosylases that recognize and remove damaged bases.
   • The resulting abasic site is processed by AP endonucleases and DNA polymerases to restore the correct sequence.

2. Nucleotide Excision Repair (NER)

   • Recognizes and removes bulky DNA adducts, such as those caused by UV light or chemical exposure.
   • Involves a multi-protein complex that unwinds the DNA and excises a short single-stranded segment containing the lesion.
   • DNA polymerase fills in the gap, followed by ligation to restore the DNA strand.

3. Mismatch Repair (MMR)

   • Corrects base-pair mismatches that occur during DNA replication.
   • Involves recognition of the mismatch, excision of the incorrect segment, and resynthesis using the correct template strand.
   • Key proteins include MutS, MutL, and MutH, which coordinate the repair process.

4. Double-Strand Break Repair (DSBR)

   • Addresses severe DNA damage where both strands of the DNA helix are broken.
   • Can be repaired through homologous recombination or non-homologous end joining.
   • Essential for maintaining genomic stability and preventing chromosomal rearrangements.

5. Direct Reversal Repair

   • A unique mechanism that directly reverses certain types of DNA damage without excision.
   • Commonly repairs O6-methylguanine lesions through the action of O6-methylguanine-DNA methyltransferase.
   • Provides a rapid and efficient way to fix specific types of damage.

6. Homologous Recombination (HR)

   • A precise repair mechanism that uses a homologous sequence as a template for repair.
   • Essential for repairing double-strand breaks and ensuring accurate DNA repair.
   • Involves key proteins such as Rad51 that facilitate strand invasion and exchange.

7. Non-Homologous End Joining (NHEJ)

   • A quicker, but less accurate, method for repairing double-strand breaks.
   • Directly ligates the broken ends of DNA without the need for a homologous template.
   • Involves proteins like Ku70/80 and DNA ligase IV, which help in recognizing and joining the ends.

8. Translesion Synthesis (TLS)

   • Allows DNA replication to continue past damaged sites by using specialized DNA polymerases.
   • These polymerases can synthesize DNA over lesions, albeit with a higher error rate.
   • Important for bypassing lesions that would otherwise stall replication forks.

9. Interstrand Crosslink Repair

   • Repairs DNA crosslinks that prevent strand separation, often caused by certain chemotherapeutic agents.
   • Involves a combination of NER and homologous recombination mechanisms.
   • Critical for maintaining DNA integrity and preventing replication stress.

10. Photoreactivation

    • A light-dependent repair mechanism that directly reverses UV-induced pyrimidine dimers.
    • Involves the enzyme photolyase, which binds to the dimer and uses light energy to cleave the bond.
    • Provides a rapid and effective way to repair UV damage without excision.