9B8T

Human polymerase epsilon bound to PCNA and DNA in the nucleotide bound state

Summary for 9B8T

• Entry DOI: 10.2210/pdb9b8t/pdb
• EMDB information: 44358
• Descriptor: DNA polymerase epsilon catalytic subunit, Proliferating cell nuclear antigen, Primer DNA, ... (7 entities in total)
• Functional Keywords: dna polymerase, dna, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 377988.28

Authors

Wang, F.,He, Q.,Li, H. (deposition date: 2024-03-31, release date: 2024-09-11, Last modification date: 2024-10-02)

Primary citation

He, Q.,Wang, F.,Yao, N.Y.,O'Donnell, M.E.,Li, H.
Structures of the human leading strand Pol epsilon-PCNA holoenzyme.
Nat Commun, 15:7847-7847, 2024

PubMed Abstract: In eukaryotes, the leading strand DNA is synthesized by Polε and the lagging strand by Polδ. These replicative polymerases have higher processivity when paired with the DNA clamp PCNA. While the structure of the yeast Polε catalytic domain has been determined, how Polε interacts with PCNA is unknown in any eukaryote, human or yeast. Here we report two cryo-EM structures of human Polε-PCNA-DNA complex, one in an incoming nucleotide bound state and the other in a nucleotide exchange state. The structures reveal an unexpected three-point interface between the Polε catalytic domain and PCNA, with the conserved PIP (PCNA interacting peptide)-motif, the unique P-domain, and the thumb domain each interacting with a different protomer of the PCNA trimer. We propose that the multi-point interface prevents other PIP-containing factors from recruiting to PCNA while PCNA functions with Polε. Comparison of the two states reveals that the finger domain pivots around the [4Fe-4S] cluster-containing tip of the P-domain to regulate nucleotide exchange and incoming nucleotide binding.

PubMed: 39245668
DOI: 10.1038/s41467-024-52257-x

Experimental method

ELECTRON MICROSCOPY (2.95 Å)