Mycobacteriophage Exploit NHEJ to Facilitate Genome Circularization

Robert S. Pitcher, Louise M. Tonkin, James M. Daley, Phillip L. Palmbos, Andrew J. Green, Tricia L. Velting, Anna Brzostek, Malgorzata Korycka-Machala, Steve Cresawn, Jaroslaw Dziadek, Graham F. Hatfull, Thomas E. Wilson, Aidan J. Doherty

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Ku-dependent nonhomologous end joining (NHEJ) is a double-strand break repair process conserved in all branches of cellular life but has not previously been implicated in the DNA metabolic processes of viruses. We identified Ku homologs in Corndog and Omega, two related mycobacteriophages of Mycobacterium smegmatis. These proteins formed homodimers and bound DNA ends in a manner identical to other Ku's and stimulated joining of ends by the host NHEJ DNA ligase (LigD). Omega and Corndog are unusual in having short 4 base cos ends that would not be expected to self-anneal and would therefore require NHEJ during phage genome circularization. Consistently, M. smegmatis LigD null strains are entirely and selectively unable to support infection by Corndog or Omega, with concomitant failure of genome circularization. These results establish a new paradigm for sequestration of the host cell NHEJ process by bacteriophage and provide a framework for understanding similar transactions in eukaryotic viral infections.

Original languageEnglish (US)
Pages (from-to)743-748
Number of pages6
JournalMolecular Cell
Volume23
Issue number5
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Keywords

  • DNA
  • MICROBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Pitcher, R. S., Tonkin, L. M., Daley, J. M., Palmbos, P. L., Green, A. J., Velting, T. L., Brzostek, A., Korycka-Machala, M., Cresawn, S., Dziadek, J., Hatfull, G. F., Wilson, T. E., & Doherty, A. J. (2006). Mycobacteriophage Exploit NHEJ to Facilitate Genome Circularization. Molecular Cell, 23(5), 743-748. https://doi.org/10.1016/j.molcel.2006.07.009