Abstract
PolD is an archaeal replicative DNA polymerase (DNAP) made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2). Recently, we reported the individual crystal structures of the DP1 and DP2 catalytic cores, thereby revealing that PolD is an atypical DNAP that has all functional properties of a replicative DNAP but with the catalytic core of an RNA polymerase (RNAP). We now report the DNA-bound cryo–electron microscopy (cryo-EM) structure of the heterodimeric DP1–DP2 PolD complex from Pyrococcus abyssi, revealing a unique DNA-binding site. Comparison of PolD and RNAPs extends their structural similarities and brings to light the minimal catalytic core shared by all cellular transcriptases. Finally, elucidating the structure of the PolD DP1–DP2 interface, which is conserved in all eukaryotic replicative DNAPs, clarifies their evolutionary relationships with PolD and sheds light on the domain acquisition and exchange mechanism that occurred during the evolution of the eukaryotic replisome.
Highlights
All forms of life have evolved multiple DNA polymerases (DNAPs) in order to maintain their genomes [1]
We describe the cryo–electron microscopy structure of a DNA-bound heterodimeric DP1–DP2 PolD complex from the archaeon Pyrococcus abyssi, revealing a unique DNA-binding site
Structure of the DP1–DP2 PolD complex bound with DNA
Summary
All forms of life have evolved multiple DNA polymerases (DNAPs) in order to maintain their genomes [1]. A wealth of structural information brought to light the molecular mechanisms evolved by B- and C-family replicative DNAPs to fulfill the processivity and fidelity requirements for copying large genomes [5,6,7]. Such structural information is missing for D-family DNAPs (PolD), which is by far the least characterized DNAP at the structural level
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