6P1H

Cryo-EM Structure of DNA Polymerase Delta Holoenzyme

Summary for 6P1H

• Entry DOI: 10.2210/pdb6p1h/pdb
• EMDB information: 20235
• Descriptor: DNA polymerase delta catalytic subunit, DNA polymerase delta small subunit, DNA polymerase delta subunit 3, ... (8 entities in total)
• Functional Keywords: dna binding, enzyme, catalysis, regulation, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 5
• Total formula weight: 243318.35

Authors

Jain, R.,Rice, W.,Aggarwal, A.K. (deposition date: 2019-05-19, release date: 2019-10-02, Last modification date: 2024-03-20)

Primary citation

Jain, R.,Rice, W.J.,Malik, R.,Johnson, R.E.,Prakash, L.,Prakash, S.,Ubarretxena-Belandia, I.,Aggarwal, A.K.
Cryo-EM structure and dynamics of eukaryotic DNA polymerase delta holoenzyme.
Nat.Struct.Mol.Biol., 26:955-962, 2019

PubMed Abstract: DNA polymerase δ (Polδ) plays pivotal roles in eukaryotic DNA replication and repair. Polδ is conserved from yeast to humans, and mutations in human Polδ have been implicated in various cancers. Saccharomyces cerevisiae Polδ consists of catalytic Pol3 and the regulatory Pol31 and Pol32 subunits. Here, we present the near atomic resolution (3.2 Å) cryo-EM structure of yeast Polδ holoenzyme in the act of DNA synthesis. The structure reveals an unexpected arrangement in which the regulatory subunits (Pol31 and Pol32) lie next to the exonuclease domain of Pol3 but do not engage the DNA. The Pol3 C-terminal domain contains a 4Fe-4S cluster and emerges as the keystone of Polδ assembly. We also show that the catalytic and regulatory subunits rotate relative to each other and that this is an intrinsic feature of the Polδ architecture. Collectively, the structure provides a framework for understanding DNA transactions at the replication fork.

PubMed: 31582849
DOI: 10.1038/s41594-019-0305-z

Experimental method

ELECTRON MICROSCOPY (3.2 Å)