6GIS

Structural basis of human clamp sliding on DNA

Replaces:  5L7C

Summary for 6GIS

• Entry DOI: 10.2210/pdb6gis/pdb
• Descriptor: Proliferating cell nuclear antigen, DNA (5'-D(P*AP*TP*AP*CP*GP*AP*TP*GP*GP*G)-3'), DNA (5'-D(P*CP*CP*CP*AP*TP*CP*GP*TP*AP*T)-3'), ... (4 entities in total)
• Functional Keywords: structural analysis human pcna dna complex sliding, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 92890.70

Authors

De March, M.,Merino, N.,Barrera-Vilarmau, S.,Crehuet, R.,Onesti, S.,Blanco, F.J.,De Biasio, A. (deposition date: 2018-05-15, release date: 2018-05-30, Last modification date: 2024-10-23)

Primary citation

De March, M.,Merino, N.,Barrera-Vilarmau, S.,Crehuet, R.,Onesti, S.,Blanco, F.J.,De Biasio, A.
Structural basis of human PCNA sliding on DNA.
Nat Commun, 8:13935-13935, 2017

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

PubMed: 28071730
DOI: 10.1038/ncomms13935

Experimental method

X-RAY DIFFRACTION (2.82 Å)