Structural basis for recruitment of translesion DNA polymerase Pol IV/DinB to the beta-clamp

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Y-family DNA polymerases replicate DNA across lesions that stall replicative polymerases.
• Their biological role necessitates regulated access to the primer-template junction to minimize mutations.
• Processivity factors, such as beta-clamp (proliferating cell nuclear antigen, PCNA), are crucial for both replicative and Y-family polymerases.

Purpose of the Study:

• To elucidate the structural basis of the interaction between the Y-family DNA polymerase Pol IV and the beta-clamp processivity factor.
• To understand how this interaction facilitates and regulates polymerase access to DNA.

Main Methods:

• X-ray crystallography was used to determine the structure of the complex between the 'little finger' domain of E. coli Pol IV and E. coli beta-clamp.
• Analysis of the crystal structure to identify interaction interfaces and conformational changes.

Main Results:

• The crystal structure reveals the complex between the 'little finger' domain of Pol IV and beta-clamp.
• A primary interaction involves a C-terminal peptide of Pol IV, consistent with known interactions.
• A substantial secondary interface was identified, positioning Pol IV in an inactive orientation.

Conclusions:

• The identified secondary interface may regulate the activity of Y-family polymerases.
• This interaction could play a role in switching between replicative and Y-family polymerases at DNA lesions.
• Structural insights into Pol IV-beta-clamp interaction provide a basis for understanding DNA repair regulation.