РЕПАРАЦИЯ НЕСПАРЕННЫХ ОСНОВАНИЙ И ПЕТЕЛЬ ДЕЛЕЦИИ/ВСТАВКИ ДНК У ЭУКАРИОТ

Abstract

The mismatch repair (MMR) system detects non-Watson – Crick base pairs as well as the defects, appearing in course of DNA replication, and helps to eliminate them by catalyzing the excision of the defect-containing region of daughter DNA and its error-free resynthesis. Thus, MMR remarkably improves the fidelity of replication. After separation, both strands contain non-repairable damages and the mismatches may generate DNA mutation in 50 % of cell progeny after next replication. MMR dysfunction causes surge of mutation rate, abnormal recombination, and cancer in humans and animals. Therefore, the main MMR efficiency parameter is mismatch correction before the next replication cycle. Mismatch detection is made by the MSH2 protein, which forms a heterodimer with either MSH6 or MSH3 (Mut S), depending on the damage (MSH6 is needed for the amendment of single base mispairs, whereas both MSH3 and MSH6 can correct IDLs). A heterodimer of MLH1 and PMS2 (Mut L) controls the interaction between the mismatch-detecting complex of proteins and other proteins essential for MMR, including exonuclease 1, helicase, nuclear antigen of proliferating cells, single-stranded DNA-binding protein and DNA polymerases δ and ε. MLH1 can form a heterodimer with two additional proteins – MLH3 and PMS1. PMS2 is required for the correction of single based mismatches, and PMS2 and MLH3 contribute to the correction of IDLs. The Nobel Prize in Chemistry 2015 was awarded for the studies of DNA repair, i.a. MMR.