Mycobacteriophage exploit NHEJ to facilitate genome circularization.

Pitcher, Robert S, Tonkin, Louise M, Daley, James M, Palmbos, Phillip L, Green, Andrew, Velting, Tricia L, Brzostek, Anna, Korycka-Machala, Malgorzata, Cresawn, Steve, Dziadek, Jaroslaw, Hatfull, Graham F, Wilson, Thomas E and Doherty, Aidan J (2006) Mycobacteriophage exploit NHEJ to facilitate genome circularization. Molecular Cell, 23 (5). pp. 743-748. ISSN 1097-2765

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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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Andrew Green
Date Deposited: 06 Feb 2012 20:47
Last Modified: 30 Nov 2012 17:08
URI: http://sro.sussex.ac.uk/id/eprint/28102
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