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I've been reading about DNA mismatch repair (MMR) and how this process improves DNA fidelity. However, I was wondering, what is stopping MMR from correcting all mistakes in the daughter DNA with 100% fidelity? Why is the error rate still around 1 in 10^9 base pairs? Is it because the MMR proteins aren't present in cells in a high enough concentration? What would you have to change about this process to achieve 100% fidelity?

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    $\begingroup$ Have you researched all the other questions on DNA repair and errors in DNA replication on this site? Please do, and then tell us why your question is not covered by them if you still need an answer. $\endgroup$
    – David
    Apr 6 at 9:23
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Nothing is 100% precise - any measurement or process allow for some error, the only difference is how often such errors occur (i.e., the probability of an error). These wildely range in biology - e.g., it is about 1 per $10^4$ in HIV replication, but only 1 per $10^9$ for human DNA (due to the repair mechanisms).

Note that $1$ in $10^9$ for human DNA means pretty much that there is about 1 error per each copying of the genome (which has the size of about $3\times10^9$). One could therefore still pose a question of why the error rate is so high? E.g., Human body consists of about $15\times10^{12}$ cells. Thus, if the error rate were about 1 per $10^{22}$($\approx 3\times10^9$ by $15\times10^{12}$), we could have human organisms consisting of the cells with identical DNA.

The answer to this is that errors are not necessarily bad: the copying errors are the source of the mutations driving the evolution! Note also that many of the errors have no effect at all on the well-being of the organism. Thus, it is fair to say that the existing error rates were selected by the evolution for assuring the appropriate rate of the evolutionary change/adaptation, without causing immediate harm to the organism. (One could even speculate that 1 error per genome copy is the appropriate rate across the organisms, but for a moment I cannot support this assertion by references).

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  • $\begingroup$ Just out of curiosity, what would be some ways to artificially decrease the error rate of DNA replication? Would increasing the concentration of MMR proteins do this? $\endgroup$ Apr 6 at 13:51
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    $\begingroup$ I do not have sufficient background in biochemistry or molecular biology to answer this - my field is more population genetics. Exposure to toxic substances or radiation are certainly important factors increasing the mutation rate (hence the cancers). $\endgroup$ Apr 6 at 14:00

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