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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 Doherty
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.

History

Publication status

  • Published

Journal

Molecular Cell

ISSN

1097-2765

Issue

5

Volume

23

Page range

743-748

Pages

6.0

Department 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

2012-02-06

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