Question

Discuss the similarities and differences between nucleotide excision repair and the mismatch repair system.

Short answer

Both Nucleotide Excision Repair (NER) and Mismatch Repair (MMR) are important for the repair of DNA damage. NER is versatile and removes bulkier, helix-distorting lesions such as those caused by UV light or cigarette smoke. MMR, on the other hand, corrects errors introduced during DNA replication. The main proteins involved in NER include XPC-RAD23B, XPA, RPA, TFIIH, XPG, and XPF-ERCC1, while those in MMR include MSH2-MSH6 (MutS alpha), MSH2-MSH3 (MutS beta), MLH1-PMS2 (MutL alpha).

Step-by-step solution

Understanding Nucleotide Excision Repair

Nucleotide Excision Repair (NER) is a highly conserved repair mechanism that is present in virtually all organisms. NER removes bulky, helix-distorting lesions like UV-induced photolesions and bulky chemical adducts. NER can act genome-wide (Global Genome NER or GG-NER) or focus on the transcribed strand of active genes (Transcription-Coupled NER or TC-NER).

Understanding Mismatch Repair

Mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage. MMR increases the fidelity of replication by an additional 20- to 400-fold.

Similarities and Differences

Both NER and MMR repair systems are instrumental in maintaining genomic stability. These mechanisms prevent the accumulation of mutations, thereby reducing the risk of disease development, including cancer. The key difference between the two is the type of errors they correct. While NER detects damage caused majorly by external factors such as UV light or cigarette smoke, MMR identifies and corrects errors introduced during DNA replication. Another significant difference is that NER is a more versatile system and can correct a wider array of distortions including bulky adducts and crosslinks, whereas MMR mainly corrects base mismatches and small insertions or deletions. The proteins involved in these processes also differ. For NER, the main proteins involved are XPC-RAD23B, XPA, RPA, TFIIH, XPG, and XPF-ERCC1, while for MMR, the key proteins are MSH2-MSH6 (MutS alpha), MSH2-MSH3 (MutS beta), MLH1-PMS2 (MutL alpha).