Year: 2020
Type: peer-review
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.
Authors: Zucai Suo, Adarsh Kumar
Institution: Florida State University
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G304302788, G4220061612, G636487281
OpenAlex ID: W4254378673