6s1o

Publication Abstract from PubMed

In eukaryotes, DNA polymerase delta (Pol delta) 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 delta-DNA-PCNA complex in the absence and presence of FEN1. Pol delta 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 delta's activity in replicating the human genome.

Structure of the processive human Pol delta holoenzyme.,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 Nat Commun. 2020 Feb 28;11(1):1109. doi: 10.1038/s41467-020-14898-6. PMID:32111820^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.