Functional eukaryotic nuclear localization signals are widespread in terminal proteins of bacteriophages

Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18482-7. doi: 10.1073/pnas.1216635109. Epub 2012 Oct 22.


A number of prokaryotic proteins have been shown to contain nuclear localization signals (NLSs), although its biological role remains sometimes unclear. Terminal proteins (TPs) of bacteriophages prime DNA replication and become covalently linked to the genome ends. We predicted NLSs within the TPs of bacteriophages from diverse families and hosts and, indeed, the TPs of Φ29, Nf, PRD1, Bam35, and Cp-1, out of seven TPs tested, were found to localize to the nucleus when expressed in mammalian cells. Detailed analysis of Φ29 TP led us to identify a bona fide NLS within residues 1-37. Importantly, gene delivery into the eukaryotic nucleus is enhanced by the presence of Φ29 TP attached to the 5' DNA ends. These findings show a common feature of TPs from diverse bacteriophages targeting the eukaryotic nucleus and suggest a possible common function by facilitating the horizontal transfer of genes between prokaryotes and eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacillus Phages / metabolism
  • Bacteriophages / metabolism*
  • COS Cells
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Chlorocebus aethiops
  • DNA, Viral / metabolism
  • Eukaryota / metabolism*
  • Gene Transfer, Horizontal
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / metabolism*
  • Prokaryotic Cells / virology
  • Protein Structure, Tertiary
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism


  • DNA, Viral
  • Nuclear Localization Signals
  • Viral Proteins