6S1O

Human polymerase delta holoenzyme Conformer 3

Summary for 6S1O

• Entry DOI: 10.2210/pdb6s1o/pdb
• Related: 6S1M 6S1N 6S1O 6TNY 6TNZ
• EMDB information: 10080 10081 10082 10539 10540
• Descriptor: DNA polymerase delta catalytic subunit, THYMIDINE-5'-TRIPHOSPHATE, DNA polymerase delta subunit 2, ... (10 entities in total)
• Functional Keywords: protein, replication
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 351433.84

Authors

Lancey, C.,Hamdan, S.M.,De Biasio, A. (deposition date: 2019-06-19, release date: 2019-12-25, Last modification date: 2024-05-22)

Primary citation

Lancey, C.,Tehseen, M.,Raducanu, V.S.,Rashid, F.,Merino, N.,Ragan, T.J.,Savva, C.G.,Zaher, M.S.,Shirbini, A.,Blanco, F.J.,Hamdan, S.M.,De Biasio, A.
Structure of the processive human Pol delta holoenzyme.
Nat Commun, 11:1109-1109, 2020

PubMed Abstract: In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ's activity in replicating the human genome.

PubMed: 32111820
DOI: 10.1038/s41467-020-14898-6

Experimental method

ELECTRON MICROSCOPY (8.1 Å)