Suppose you are studying two mutant strains of E. coli that are deficient in DNA

Question

Suppose you are studying two mutant strains of E. coli that are deficient in DNA replication. One mutant strain is known to have no DNA ligase and the other mutant strain is known to have no DNA polymerase I, but in both cases the other enzymes involved in DNA replication are normal. The DNA synthesized on the "LAGGING STRAND" from both mutants is found to be largely similar in characteristics, but there is also a difference in their characteristics when the two strains are compared. How would you expect the lagging strand DNA from the two mutant strains to be similar and how would they differ from each other?

Explanation / Answer

The stability of complex and highly organized nuclear genomes partly depends on the ability of mismatch repair (MMR) to correct a variety of different mismatches generated as the leading and lagging strand templates are copied by three polymerases, each with different fidelity. Here we provide the first comparison, to our knowledge, of the efficiency of MMR of leading and lagging strand replication errors. We first confirm that Pol e is the primary leading strand replicase, complementing earlier assignment of Pols a and d as the primary lagging strand replicases. We then show that MMR efficiency in vivo strongly depends on the polymerase that generates the mismatch and on the composition and location of mismatches. In one extreme case, a flanking triplet repeat sequence eliminates MMR altogether. Overall, MMR is most efficient for mismatches generated at the highest rates and having the most deleterious potential, thereby ultimately achieving high-fidelity replication of both DNA strands.

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