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Contributed by Charles C. Richardson, February 2, 2017 (sent for review January 9, 2017; reviewed by Ulrich Hübscher and Margarita Salas)
Significance
Most DNA polymerases initiate DNA synthesis by extending a preexisting primer. Exceptions to this dogma are recently characterized bifunctional primase–polymerases (prim–pols) that resemble archaeal primases in their structure and initiate DNA synthesis de novo using only NTPs or dNTPs. We report here a DNA polymerase encoded by a phage NrS-1 from deep-sea vents. NrS-1 has a genome organization unlike any other known phage. Although this polymerase does not contain a zinc-binding motif typical for primases, it is nonetheless able to initiate DNA synthesis from a specific DNA sequence exclusively using dNTPs. Thus, it represents a unique de novo replicative DNA polymerase that possesses features found in DNA polymerases, primases, and RNA polymerases.
Abstract
A DNA polymerase is encoded by the deep-sea vent phage NrS-1. NrS-1 has a unique genome organization containing genes that are predicted to encode a helicase and a single-stranded DNA (ssDNA)-binding protein. The gene for an unknown protein shares weak homology with the bifunctional primase–polymerases (prim–pols) from archaeal plasmids but is missing the zinc-binding domain typically found in primases. We show that this gene product has efficient DNA polymerase activity and is processive in DNA synthesis in the presence of the NrS-1 helicase and ssDNA-binding protein. Remarkably, this NrS-1 DNA polymerase initiates DNA synthesis from a specific template DNA sequence in the absence of any primer. The de novo DNA polymerase activity resides in the N-terminal domain of the protein, whereas the C-terminal domain enhances DNA binding.
Footnotes
- ↵1To whom correspondence may be addressed. Email: ccr{at}hms.harvard.edu or Bin_Zhu{at}hust.edu.cn.
Author contributions: B.Z. and C.C.R. designed research; B.Z., L.W., H.M., and X.L. performed research; A.J.H., Y.Y.-T., and T.N. contributed new reagents/analytic tools; B.Z., S.T., and C.C.R. analyzed data; and B.Z., L.W., A.J.H., Y.Y.-T., T.N., S.T., and C.C.R. wrote the paper.
Reviewers: U.H., University of Zurich; and M.S., Consejo Superior de Investigaciones Científicas (CSIC).
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1700280114/-/DCSupplemental.
De novo DNA polymerase from deep-sea vent
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