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Updated: Apr 19, 2026

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
Genome-wide survey and phylogenetic analysis on subunit sequences of eukaryotic DNA polymerase delta
Abstract:
DNA polymerase d is not only the major replicative enzyme in eukaryotic chromosomal DNA synthesis but is also the primary polymerase for most DNA repair pathways. However, the subunit composition of polymerase d varies in different organisms. While polymerase d in many eukaryotic species has all 4 subunits (POLD1, 2, 3, and 4), many other organisms do not possess POLD4. Whether POLD4 is indispensable and why these differences exist are unknown. In the present study, we identified the POLD4 protein sequences of 218 eukaryotic species and determined the POLD1, 2, and 3 protein sequences of 55 species representing various taxonomic groups. No insect and nematode species examined possessed POLD4. Approximately 80% of protozoan species did not contain POLD4. Nearly 50% of fungal species did not contain POLD4. Other animal and plant species are expected to contain POLD4. Phylogenetic analyses of POLD1, 2, 3, and 4 sequences revealed that most animal and plant species inherited DNA polymerase d from protozoa, whereas some other animal and plant species may have inherited polymerase d directly from fungi. Because a large number of protozoan and fungal species do not possess POLD4, current insect and nematode species lacking POLD4 may have evolved from ancestor protozoan species lacking POLD4; thus, other protozoan and animal species lacking POLD4 may share a similar evolutionary history. Future studies should examine the origin and indispensability of POLD4 in various organisms.
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