DNA mismatch repair

DNA mismatch repair

Mismatch repair is a type pf DNA repair mechanism in which consists in the repair of a DNA strand that has suffered a alteration in a nucleotide. These changes occur only when replication occurs and in daughter DNA strands only. Furthermore, these changes are not mutagenic, meaning that the altered nucleotides possess the same base match properties of the “normal” nucleotides, making them harder to distinguish from “normal” base matches.  

Since this type of damage/error is not easily detected, it is necessary to distinguish daughter DNA strand, in which occurs the nucleotide alteration, from mother DNA strand . In E. coli, mother DNA strands are methylated, meaning that these strands have methyl groups, unlike daughter strands, which have not. Mother strands are methylated due to DNA adenine methylase, enzyme that convert adenines to 6-methyladenines in the sequence 5′-GATC-3′, and DNA cytosine methylase, enzyme that converts cytosine to 5-methylcytosines in the sequences 5′-CCAGG-3′ and 5′-CCTGG-3′. 

The methylation process does not occur immediately after replication. It takes some time for the daughter strand to be methylated after being created, making a time window long enough for the mismatch repair process to take place.

In E. coli, there are three types of mismatch repairs:

·         long patch -> the DNA that is repaliced can be over 1kb long and utilizes enzymes MutH, Muts and MutL, along with DNA helicase II. MutH recognizes the undermethylated strand (daughter strand) by binding to undermethylated 5′-GATC-3′ sequences and MutS binds to the mismatch zone. It is unclear the role of MutL in the process, but it may somehow coordinate the other two proteins, so that MutH binds only to 5′-GATC-3′ sequences in the proximity of the mismatch zone recognized by MutS. After binding, MutH cuts the phosphodiester bond immediately upstream of the G nucleotide of the 5′-GATC-3′ sequence and DNA helicase II separates the single strand. The region originated from this process is degenerated by an exonuclease. This leaves a blank in the DNA sequence which is filled by DNA created by DNA polymerase I and DNA ligase;

·         short patch -> the events that occur in this type of repair are similar, the difference lying in the specificities of proteins involved in the recognition of the mismatch and the size of the replaced strand, of about 10bp long;

·         very short patch -> similar to short strand, but different enzymes and shorter strand.  

               It seems necessary to warn that these processes were study in E. coli. In mammals, mismatch repair was proved to exist, but the methylated chains are short, which puts the strand identification method mentioned above in cause.