Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Proliferating cell nuclear antigen (PCNA) is essential for eukaryotic DNA replication, acting as a processivity factor for DNA polymerase delta.
• Understanding PCNA's structure is crucial for elucidating the mechanisms of DNA replication in eukaryotes.

Purpose of the Study:

• To determine the crystal structure of Saccharomyces cerevisiae PCNA.
• To understand how PCNA interacts with DNA and facilitates polymerase activity.

Main Methods:

• X-ray crystallography was used to determine the crystal structure of S. cerevisiae PCNA.
• The structure was resolved at 2.3 Å resolution.

Main Results:

• The crystal structure revealed that PCNA forms a trimeric ring composed of two identical domains per monomer.
• The PCNA ring is a closed structure with dimensions and electrostatic properties suitable for encircling duplex DNA.
• A striking structural similarity was observed between the trimeric eukaryotic PCNA ring and the dimeric bacterial PCNA ring (beta subunit of E. coli DNA polymerase III holoenzyme), despite no significant sequence identity.

Conclusions:

• The PCNA ring likely encircles DNA, forming a platform for DNA polymerase attachment.
• The structural similarity between eukaryotic and prokaryotic PCNA rings supports a conserved mechanism for DNA replication processivity.
• This finding provides structural evidence for the mechanistic link between eukaryotic and prokaryotic DNA replication.