Abstract
B-family DNA polymerases (PolBs) represent the most common replicases. PolB enzymes that require RNA (or DNA) primed templates for DNA synthesis are found in all domains of life and many DNA viruses. Despite extensive research on PolBs, their origins and evolution remain enigmatic. Massive accumulation of new genomic and metagenomic data from diverse habitats as well as availability of new structural information prompted us to conduct a comprehensive analysis of the PolB sequences, structures, domain organizations, taxonomic distribution and co-occurrence in genomes. Based on phylogenetic analysis, we identified a new, widespread group of bacterial PolBs that are more closely related to the catalytically active N-terminal half of the eukaryotic PolEpsilon (PolEpsilonN) than to Escherichia coli Pol II. In Archaea, we characterized six new groups of PolBs. Two of them show close relationships with eukaryotic PolBs, the first one with PolEpsilonN, and the second one with PolAlpha, PolDelta and PolZeta. In addition, structure comparisons suggested common origin of the catalytically inactive C-terminal half of PolEpsilon (PolEpsilonC) and PolAlpha. Finally, in certain archaeal PolBs we discovered C-terminal Zn-binding domains closely related to those of PolAlpha and PolEpsilonC. Collectively, the obtained results allowed us to propose a scenario for the evolution of eukaryotic PolBs.
Highlights
Cellular replicative DNA polymerases (Pols) are classified into three families of non-homologous enzymes, PolB, PolC and PolD, that synthesize DNA at the replication forks of eukaryotes, bacteria and most archaea, respectively [1,2]
We have previously shown that PhiKZ phages encode a divergent homolog of the phage T4 DNA polymerase [3]
We modeled the structure of experimentally characterized B2 member (AAK41686) from S. solfataricus P2 [25]
Summary
Cellular replicative DNA polymerases (Pols) are classified into three families of non-homologous enzymes, PolB, PolC and PolD, that synthesize DNA at the replication forks of eukaryotes, bacteria and most archaea, respectively [1,2]. PolBs are the most widespread, found in all domains of life and several lineages of DNA viruses [3]. PolBs can be subdivided into three major apparently monophyletic assemblages based on the primer they use. Protein-primed PolBs (pPolBs) replicate small linear genomes of viruses and selfish mobile genetic elements [4,5,6]. The PolBs that require a pre-existing nucleic acid (RNA or DNA) primer participate in genome replication and repair in all living organisms and their viruses [3]. The third assemblage includes the recently identified group of primer-independent PolBs (piPolBs) encoded by bacterial and mitochondrial mobile genetic elements and capable of template-dependent de novo DNA synthesis [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
