ID #2430

One of our homework problems say: "A certain organism, Errorproniuous higheras, has a typical error frequency of 2 mistakes every cell division. One clustered group of atypical cells of this multicellular organism was found to have an error frequency of 200 mistakes per cell division. Which one of the following explanations for this observation is most likely? Incorrect: That cell cluster is missing error-prone repair mechanisms. Correct: The proofreading enzymes are missing in that cell cluster. Incorrect: That cell cluster has stopped dividing. Incorrect: Both the proofreading and mismatch repair enzymes are missing in that cell cluster. Incorrect: Nothing has happened to that cell cluster." As you can see, the apparent correct answer is the second choice. However, I was under the impression that in order for a cell to divide, which the question implies that these cells are doing, a cell must first replicate its DNA. This would require the presence of DNA polymerases. Option two seems to imply that the cell cluster with more errors is missing its DNA polymerases, which are the proofreading enzymes. If the cell cluster with more errors was missing its DNA polymerases, how would it be able to replicate and divide? If it can't under the conditions given in option two, then option two seems to be a very unlikely explanation of the observations, since in the question we can clearly see that these cells are dividing. So to me, option one seemed the most likely of the choices given. Am I just completely wrong or confused here?

Thank you for explaining your thought process on this question- I think you were on the right track. I think you may have over-thought things when analyzing your answer choices. First, proofreading is usually performed by DNA polymerases, as you point out. In Lecture 23, Prof. Mehrtens mentioned in class that in the absence of proofreading activity, the error frequency is 100x higher. A cell without mismatch repair also makes 100x more mistakes. If a cell lacks both proofreading and mismatch repair, the error frequency is 10,000x (100 x 100) higher. In Question 2, the error frequency increases from 2 mistakes to 200 mistakes in the atypical cells, which is a 100-fold increase in errors. This would suggest that either proofreading or mismatch repair are missing, so proofreading is the correct answer (since mismatch repair by itself was not one of your answer choices). 
It is possible to separate the polymerase activity of DNA polymerases from the 3' to 5' exonuclease activity of the same polymerases. DNA polymerases have multiple subunits, and theoretically a mutation in the subunit that has the 3' to 5' exonuclease activity would not affect the rest of the enzyme (including the polymerase activity), so replication could proceed (albeit without proofreading). In research, there are commercially available purified DNA polymerases that lack 3' to 5' exonuclease activity, since some applications work better with polymerases that cannot proofread. For the first answer choice, error prone repair is only turned on under certain circumstances and a cell without error prone repair (but with proofreading and mismatch repair intact) would make less errors. A cell without error prone repair would be also more apt to die under stressful conditions because error prone repair is a last-ditch effort to maintain as much genomic integrity as possible. 
In this case, the best answer to the question is the second choice. 

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