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Structure of the processive human Pol δ holoenzyme.

<div class='caption-title'>Cryo-EM structure of the processive Pol δ–DNA–PCNA complex.</div>
<div class='caption-title'>Cryo-EM density and model of selected regions of the Pol δ–DNA–PCNA complex.</div>
<div class='caption-title'>Interaction of the processive Pol δ holoenzyme with DNA.</div>
Lancey C, Tehseen M, Raducanu VS, Rashid F, Merino N, Ragan TJ, Savva CG, Zaher MS, Shirbini A, Blanco FJ, Hamdan SM, De Biasio A
OpenAccess logo Nat Commun 11 1109 (2020)
Related entries: 6s1m, 6s1o, 6tny, 6tnz

Cited: 70 times
EuropePMC logo PMID: 32111820

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.

Articles - 6s1n mentioned but not cited (1)

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Reviews citing this publication (14)

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