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Mycobacteriophage exploit NHEJ to facilitate genome circularization.
journal contribution
posted on 2023-06-08, 07:48 authored by Robert S Pitcher, Louise M Tonkin, James M Daley, Phillip L Palmbos, Andrew Green, Tricia L Velting, Anna Brzostek, Malgorzata Korycka-Machala, Steve Cresawn, Jaroslaw Dziadek, Graham F Hatfull, Thomas E Wilson, Aidan DohertyAidan DohertyKu-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.
History
Publication status
- Published
Journal
Molecular CellISSN
1097-2765External DOI
Issue
5Volume
23Page range
743-748Pages
6.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
AD directed the research and was the corresponding author. This paper reports the discovery of a mechanism of phage genome circularization that involves the usurping of the bacterial host DNA break-repair machinery and establishing a new paradigm for understanding how similar transactions occur during eukaryotic viral infections.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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