Outline the steps in which MutS MutL and MutH identify and r

Outline the steps in which MutS, MutL, and MutH identify and repair mismatches in DNA. How does this system ensure that the nucleotide that is replaced is the erroneous one and not the original nucleotide in the template DNA? (Please provide your answer in your own words and understandable as I need to understand this for an upcoming exam)

Solution

The mismatch is recognized by MutS. MutS dimer recognizes the mismatched base on the daughter DNA strand and binds to the mutated DNA. MutH is now recruited and it binds at the hemimethylated DNA on the daughter strand of DNA. However MutH is activated only after the binding of MutL dimer to the MutS-DNA complex. Once activated, MutH nicks the daughter DNA strand at the hemimethylated sites. MutL mow recruits UvrD helicase, also known as DNA helicase II, which unwinds the 2 DNA strands in a 3\' to 5\' direction. The MutSHL complex slides on the DNA strand in the direction of mismatch during which process the mismatched DNA strand is liberated and excised by exonucleases. If MutH makes a nick on the 5\' end of the mismatch RecJ or ExoVII 5\' to 3\' exonucleases are used. If the nick made by MutH is on the 3\' side of the mismatch ExoI which is a 3\' to 5\' exonuclease is used. Once the DNA is excised past through the mismatch, DNA polymerase III assisted by single strand binding protein adds the correct nucleotides using the other strand as template and finally DNA ligase enzyme seals the nick.

The system ensures that the nucleotide that is replaced is the erroneous one and not the original nucleotide in the template DNA by distinguishing the newly synthesized daughter strand from the template strand. This is achieved by the methylation status on the DNA strands.Template DNA is methylated while the newly synthesized daughter strand is unmethylated. In eukaryotes, the newly synthesized DNA lagging strand has transient nicks that provide signal to the mismatch repair machinery and directs the repair machinery to the appropriate strand.