Structural basis of human PCNA sliding on DNA

• DOI: 10.1038/ncomms13935
• Publication Date: 2017-01-10T10:47:45Z
• Authors: Matteo De March; Nekane Merino; Susana Barrera-Vi...; Ramon Crehuet; Silvia Onesti; Francisco J. Blanco; Alfredo De Biasio
• Keywords: DNA clamp; DNA polymerase delta; Processivity; DNA polymerase II; Clamp; Replication protein A

Abstract Sliding clamps encircle DNA and tether polymerases other factors to the genomic template. However, molecular mechanism of clamp sliding on is unknown. Using crystallography, NMR dynamics simulations, here we show that human PCNA recognizes through a double patch basic residues within ring channel, arranged in right-hand spiral matches pitch B-DNA. We propose slides by tracking backbone via ‘cogwheel’ based short-lived polar interactions, which keep orientation invariant relative DNA. Mutation at PCNA–DNA interface has been shown impair initiation synthesis polymerase δ (pol δ). Therefore, our findings suggest correctly oriented necessary for assembly replication-competent PCNA-pol holoenzyme.