Episode 147: Genetic Mutation and Repair

Base Excision

Base excision repair (BER) is a crucial mechanism for fixing small, non-helix distorting lesions in DNA. James Fodor explains that DNA glycosylases detect and remove abnormal bases, creating an AP site, which is then processed by other enzymes to restore the correct base 1. This process relies on the complementary DNA strand to ensure accuracy. However, if the complementary site is also altered, the repair may lock in a mutation 2.

   

Mismatch Repair

Mismatch repair (MMR) corrects errors that occur during DNA replication. Fodor describes how enzymes detect mismatches by identifying bulges in the DNA structure and recruit other enzymes to form a complex that removes a section of the newly synthesized strand 3. The system assumes the unmethylated strand is incorrect and replaces it based on the complementary strand 4. This method ensures that replication errors are corrected efficiently.

   

Double-Strand Breaks

Double-strand break repair (DSBR) involves complex mechanisms to fix breaks in both DNA strands. Fodor outlines two main methods: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ simply ligates the broken ends together, while HR uses a homologous chromosome to ensure accurate repair 5. This redundancy in repair mechanisms highlights the cell's efficiency in maintaining genetic integrity 6.