Structural basis of human PCNA sliding on DNA

Matteo De March, Nekane Merino, Susana Barrera-Vilarmau, Ramon Crehuet, Silvia Onesti, Francisco J. Blanco, Alfredo De Biasio

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.
Original languageEnglish (US)
JournalNature Communications
StatePublished - Jan 10 2017
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Chemistry
  • General Physics and Astronomy


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