Polymerase dynamics at the eukaryotic DNA replication fork.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• DNA polymerases (Pol) delta and epsilon are crucial for eukaryotic DNA replication.
• Their specific roles in leading and lagging strand synthesis have been debated.
• Understanding their functions is vital for comprehending genome stability.

Purpose of the Study:

• To review recent insights into the distinct roles of Pol delta and Pol epsilon in eukaryotic DNA replication.
• To elucidate their functions in both undisturbed replication and Okazaki fragment maturation.
• To highlight new evidence supporting their strand-specific assignments.

Main Methods:

• Review of recent scientific literature and experimental findings.
• Analysis of data from polymerase mutants exhibiting asymmetric mutator phenotypes.
• Examination of mechanisms involved in Okazaki fragment initiation and maturation.

Main Results:

• Pol epsilon is identified as the leading strand polymerase, and Pol delta as the lagging strand polymerase.
• Pol delta corrects errors made by Pol alpha during Okazaki fragment initiation.
• The strand displacement synthesis by Pol delta dictates the Okazaki fragment maturation pathway (short/long flap).

Conclusions:

• The distinct roles of Pol epsilon (leading strand) and Pol delta (lagging strand) in DNA replication are increasingly supported.
• Pol delta plays a critical role in lagging strand synthesis fidelity and Okazaki fragment processing.
• The interplay between Pol delta, FEN1, and Dna2 is essential for efficient RNA removal during Okazaki fragment maturation.