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Mycobacteriophage Exploit NHEJ to Facilitate Genome Circularization

Pitcher, RS and Tonkin, LM and Daley, JM and Palmbos, PL and Green, AJ and Velting, TL and Brzostek, A and Korycka-Machala, M and Cresawn, S and Dziadek, J and Hatfull, GF and Wilson, TE and Doherty, AJ (2006) Mycobacteriophage Exploit NHEJ to Facilitate Genome Circularization. Molecular Cell, 23 (5). 743 - 748. ISSN 1097-2765

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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. © 2006 Elsevier Inc. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pitcher, RS
Tonkin, LM
Daley, JM
Palmbos, PL
Green, AJ
Velting, TL
Brzostek, A
Korycka-Machala, M
Cresawn, S
Dziadek, J
Hatfull, GFgfh@pitt.eduGFH
Wilson, TE
Doherty, AJ
Date: 1 September 2006
Date Type: Publication
Journal or Publication Title: Molecular Cell
Volume: 23
Number: 5
Page Range: 743 - 748
DOI or Unique Handle: 10.1016/j.molcel.2006.07.009
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
ISSN: 1097-2765
MeSH Headings: Antigens, Nuclear--metabolism; Bacterial Proteins--metabolism; DNA Ligases--metabolism; DNA, Bacterial--metabolism; DNA, Circular--genetics; DNA, Circular--metabolism; DNA-Binding Proteins--metabolism; Genome--genetics; Mycobacteriophages--genetics; Mycobacterium smegmatis--cytology; Mycobacterium smegmatis--virology; Nucleic Acid Conformation; Recombination, Genetic; Saccharomyces cerevisiae--metabolism
PubMed ID: 16949369
Date Deposited: 05 Dec 2012 16:30
Last Modified: 02 Feb 2019 15:57


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