2024-03-28T18:34:55Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1425392021-12-27T16:26:29Zcom_10261_5063com_10261_5col_10261_5066
De March, Matteo
Merino, Nekane
Barrera-Vilarmau, Susana
Creuhet, Ramon
Onesti, Silvia
Blanco, Francisco J.
De Biasio, Alfredo
2017-01-16T11:36:45Z
2017-01-16T11:36:45Z
2017-01-10
Nature Communications 8: Article number: 13935 (2017)
http://hdl.handle.net/10261/142539
10.1038/ncomms13935
http://dx.doi.org/10.13039/501100003329
28071730
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.
eng
openAccess
DNA metabolism
Holoenzymes
Replisome
Structural basis of human PCNA sliding on DNA
artículo