Mutations

ID #1249

I was wondering about the mismatch repair system. I understand the hemimethylation and the palindromic sequence..etc. I am confused about the actual mechanism. Can you explain the steps that the enzymes go through between the three enzyme mutH, mutL and mutS, and how it creates that U shape, and the cleavage etc? A couple of specific questions: how many bases are cleaved out by the enzyme, and is that an always number or approximate number, is the L what causes the U shape, how do H and S communicate, and what role does each enzyme play, and what is the purpose of the loop?


You definitely don't have to know the names or roles of the individual molecules in the mismatch repair system, so don't worry about MutS, MutH, and MutL. At a fundamental level, here's what you do have to know. The mismatch repair has two separate, but related "jobs." One is to recognize a problem (called a lesion), the second is to identify which strand to "fix." So first, a mismatched base pair is recognized by one component of the system, and it holds its place. Next, another member of the system goes looking for the nearest hemimethylated GATC sequence, which might be on either "side" of the problem. Now these two regions, which might be separated by as many as a thousand bases, are brought togther by a "linker" protein, looping out the region of DNA in between in the process. That's where that "U" shape comes from, and it's not always the same length. The linking of all these members acts as a "trigger" that says it's ok to start stripping out a region of DNA on the daughter strand through the "U" shaped loop until it gets just past the lesion. Then that region is replaced and ligated, and the members of the system go looking for any additional problems.

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