Mutations

ID #2428

I have a question involving mismatch repair: When Professor Mehrtens mentioned that the methylase enzyme comes and scans for a particular sequence (GATC), adding a methyl group to the A, is this referring to the newly synthesized strand or the parent strand? I know that the parent strand is methylated, whereas the daughter strand isn't. What exactly is methylated - is it only the A's in E.coli and G/C's in humans? or is the whole parent strand methylated? I wrote in my notes: "If the parent strand is methylated and the newly synthesized strand is not, we need to fix the non-methalyated stand." Could you please clear that up for me?


The parent strand of DNA would already be methylated by the time of DNA replication. The newly synthesized DNA is the one that must be methylated. This doesn't happen instantly as soon as the new strand is made; it takes some time for the methylase to finish adding methyl groups to all the As. 
You are correct that the A of the GATC sequence is methylated in E. coli and the C of CGs in humans. To be clear, though, not every base in the parent strand is methylated. 
The sentence you quote from your notes would be in the case of a mismatch. Based on just the mismatch, the proteins in the cell can't tell which strand is "right" so they don't know which base to cut out and replace. But the methylation (or lack thereof) provides a guide. The parent strand is methylated and therefore assumed to be right. The new strand is not methylated, so the proteins know that the new strand is probably the one with the mistake. The MutL, MutS, and MutH proteins discussed in lecture actually carry out this mismatch repair process. 

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