Differential correction of lagging-strand replication errors made by DNA polymerases {alpha} and {delta}

Area of Science:

• Molecular Biology
• Genetics
• DNA Replication and Repair

Background:

• DNA mismatch repair (MMR) corrects replication errors but requires DNA ends for strand discrimination.
• The source of these ends in vivo is largely unknown, except in organisms using adenine methylation.
• A hypothesis suggests MMR interacts with the replication complex to use DNA ends as strand signals.

Purpose of the Study:

• To investigate the hypothesis that DNA ends associated with replication are used for strand discrimination in MMR.
• To compare MMR efficiency for errors made by yeast DNA polymerase α (Pol α) and DNA polymerase δ (Pol δ).

Main Methods:

• Comparison of Msh2-dependent mismatch repair (MMR) efficiency.
• Utilizing variant forms of yeast DNA polymerase α (Pol α) and DNA polymerase δ (Pol δ).
• Analyzing MMR efficiency for replication errors introduced by these polymerases.

Main Results:

• MMR efficiency was consistently higher for mismatches created by Pol α compared to Pol δ.
• Exonuclease-deficient Pol α, which is less accurate, showed higher Msh2-dependent repair efficiencies.
• This indicates MMR is more efficient for errors from the less accurate replicative polymerase.

Conclusions:

• MMR demonstrates a special relationship with the replication complex.
• The 5' ends of Okazaki fragments likely serve as strand discrimination signals for MMR.
• This proximity may enhance Msh2-dependent MMR through 5' excision or strand displacement mechanisms.