8D3R

Human mitochondrial DNA polymerase gamma ternary complex with GT basepair in intermediate conformer

Summary for 8D3R

• Entry DOI: 10.2210/pdb8d3r/pdb
• EMDB information: 27154 27155 27163 27169 27170 27171 27172
• Descriptor: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2, mitochondrial, DNA (5'-D(P*AP*AP*AP*AP*CP*GP*AP*CP*GP*GP*CP*CP*AP*GP*TP*GP*CP*CP*AP*TP*AP*T)-3'), ... (6 entities in total)
• Functional Keywords: dna-binding protein, dna polymerase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 266237.26

Authors

Park, J.,Yin, Y.W. (deposition date: 2022-06-01, release date: 2023-05-24, Last modification date: 2024-10-30)

Primary citation

Park, J.,Herrmann, G.K.,Mitchell, P.G.,Sherman, M.B.,Yin, Y.W.
Pol gamma coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.
Nat.Struct.Mol.Biol., 30:812-823, 2023

PubMed Abstract: Accurate replication of mitochondrial DNA (mtDNA) by DNA polymerase γ (Polγ) is essential for maintaining cellular energy supplies, metabolism, and cell cycle control. To illustrate the structural mechanism for Polγ coordinating polymerase (pol) and exonuclease (exo) activities to ensure rapid and accurate DNA synthesis, we determined four cryo-EM structures of Polγ captured after accurate or erroneous incorporation to a resolution of 2.4-3.0 Å. The structures show that Polγ employs a dual-checkpoint mechanism to sense nucleotide misincorporation and initiate proofreading. The transition from replication to error editing is accompanied by increased dynamics in both DNA and enzyme, in which the polymerase relaxes its processivity and the primer-template DNA unwinds, rotates, and backtracks to shuttle the mismatch-containing primer terminus 32 Å to the exo site for editing. Our structural and functional studies also provide a foundation for analyses of Polγ mutation-induced human diseases and aging.

PubMed: 37202477
DOI: 10.1038/s41594-023-00980-2

Experimental method

ELECTRON MICROSCOPY (3.04 Å)