Secret From The Abyss: Structures Of The D-Family Dna Polymerase (Pold) Reveal That Dna Replication And Dna Transcription Share A Joint Evolutionary History In Archaea

Archaeal replicative DNA polymerases D (PolD) constitute an atypical class of DNA polymerases made of a proof-reading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2), both with unknown structures. We have determined crystal structures of Pyrococcus abyssi PolD, revealing a catalytic core strikingly different from all other known DNA polymerases (DNAPs). Rather, the PolD DP2 catalytic core has the same “double-psi β-barrel” architecture seen in the RNA polymerase (RNAP) superfamily, which includes multi-subunit transcriptases of all domains of life, homodimeric RNA silencing pathway RNAPs and atypical viral RNAPs. This finding bridges together, for the first time in cellular life, DNA transcription and DNA replication within the same protein superfamily. This study documents further the complex evolutionary history of the DNA replication apparatus in different kingdoms of life and proposes a novel paradigm on the classification of all extant DNAPs.