The Y-Family of DNA Polymerases

Abstract

Based on phylogenetic relationships, DNA polymerases can be broadly classified into five families (Ito and Braithwaite 1991Ito J. Braithwaite D.K. Compilation and alignment of DNA polymerase sequences.Nucleic Acids Res. 1991; 19: 4045-4057Crossref PubMed Scopus (276) Google Scholar, Braithwaite and Ito 1993Braithwaite D.K. Ito J. Compilation, alignment, and phylogenetic relationships of DNA polymerases.Nucleic Acids Res. 1993; 21: 787-802Crossref PubMed Scopus (521) Google Scholar). The A-family is typified by Escherichia coli DNA polymerase I (pol I); the B-family by E. coli pol II; the C-family by the E. coli pol III α-catalytic subunit; the D-family by archeal polymerases (Cann and Ishino 1999Cann I.K. Ishino Y. Archaeal DNA replication identifying the pieces to solve a puzzle.Genetics. 1999; 152: 1249-1267Crossref PubMed Google Scholar); and the X-family by eukaryotic pol β. Recently, a large number of new DNA polymerases have been identified, which although sharing significant amino acid sequence identity and similarity amongst themselves, exhibit little homology to any of the five previously identified polymerase families. This new family of polymerases has been described in the literature as the UmuC/DinB/Rev1/Rad30 superfamily. At the present time, these enzymes are best characterized in terms of their low-fidelity synthesis on undamaged DNA and their ability to bypass DNA lesions in vitro which normally block replication by members of the A-, B-, C-, D-, or X-family of polymerases. In keeping with the original suggestion of Ito and Braithwaite that related enzymes be identified by a distinct “family name”(Ito and Braithwaite 1991Ito J. Braithwaite D.K. Compilation and alignment of DNA polymerase sequences.Nucleic Acids Res. 1991; 19: 4045-4057Crossref PubMed Scopus (276) Google Scholar), we formally propose that henceforth the UmuC/DinB/Rev1/Rad30 DNA polymerases be referred to as the “Y-family” of DNA polymerases. Phylogenetic analysis of the Y-family of DNA polymerases reveals several branches to an unrooted tree (Figure 1). Interestingly, not all branches are evenly distributed amongst the three kingdoms of life. The UmuC family, typified by E. coli pol V, appears to be found exclusively in prokaryotes and has separate branches in gram-negative and gram-positive bacteria. The DinB branch is the most widely distributed and is present in bacteria, eukaryotes, and archaea. In E. coli, the DinB protein is called pol IV, while in humans the product of the DINB1 gene has been designated as both polθ and polκ. Indeed, the rapid pace with which new DNA polymerases have been discovered has led to some confusion in the literature concerning the nomenclature of certain eukaryotic DNA polymerases, notably polθ and polκ, where multiple proteins have been given the same Greek letter designation. This topic will be the subject of a more detailed discussion elsewhere (P. Burgers, personal communication). While DinB is ubiquitous, it is not essential for life and is notably absent in the completely sequenced genomes of Saccharomyces cerevisiae and Drosophila melanogaster. In contrast, the Rev1-like proteins are absent in bacteria and archaea and are only found in eukaryotes. Analysis of the Rad30 branch suggests that it too is only found in eukaryotes but is quite diverse and can be subdivided into two further subfamilies. One of these is represented by the RAD30/RAD30A gene, which encodes DNA polη, a polymerase with biochemical properties conserved from S. cerevisiae to humans. A second subfamily, which is found exclusively in higher eukaryotes, is represented by RAD30B encoding DNA polι. The phylogenetic tree presented in Figure 1 is compiled from 52 proteins. It is taken for granted that this number will grow significantly as the genomes of more organisms are sequenced in their entirety. We suggest, therefore, that proteins related to this ever-growing family of proteins be identified as members of the Y-family of DNA polymerases. We would like to thank Tomoo Ogi for generating the unrooted phylogenetic tree shown in Figure 1 and Junetsu Ito for his comments on our proposal.