New insights into the structures and interactions of bacterial Y-family DNA polymerases

Nucleic Acids Res. 2019 May 21;47(9):4393-4405. doi: 10.1093/nar/gkz198.

Abstract

Bacterial Y-family DNA polymerases are usually classified into DinB (Pol IV), UmuC (the catalytic subunit of Pol V) and ImuB, a catalytically dead essential component of the ImuA-ImuB-DnaE2 mutasome. However, the true diversity of Y-family polymerases is unknown. Furthermore, for most of them the structures are unavailable and interactions are poorly characterized. To gain a better understanding of bacterial Y-family DNA polymerases, we performed a detailed computational study. It revealed substantial diversity, far exceeding traditional classification. We found that a large number of subfamilies feature a C-terminal extension next to the common Y-family region. Unexpectedly, in most C-terminal extensions we identified a region homologous to the N-terminal oligomerization motif of RecA. This finding implies a universal mode of interaction between Y-family members and RecA (or ImuA), in the case of Pol V strongly supported by experimental data. In gram-positive bacteria, we identified a putative Pol V counterpart composed of a Y-family polymerase, a YolD homolog and RecA. We also found ImuA-ImuB-DnaE2 variants lacking ImuA, but retaining active or inactive Y-family polymerase, a standalone ImuB C-terminal domain and/or DnaE2. In summary, our analyses revealed that, despite considerable diversity, bacterial Y-family polymerases share previously unanticipated similarities in their structural domains/motifs and interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Catalytic Domain / genetics
  • Computational Biology
  • Cytoskeleton / chemistry
  • Cytoskeleton / genetics
  • DNA Polymerase III / chemistry
  • DNA Polymerase III / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / classification
  • DNA-Directed DNA Polymerase / genetics*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics*
  • Models, Molecular
  • Protein Conformation*
  • Rec A Recombinases / chemistry
  • Rec A Recombinases / genetics*

Substances

  • DNA-Binding Proteins
  • DinB protein, E coli
  • Escherichia coli Proteins
  • recA protein, E coli
  • UmuC protein, E coli
  • DNA polymerase III, alpha subunit
  • Rec A Recombinases
  • DNA Polymerase III
  • DNA-Directed DNA Polymerase